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Sample records for gene polymorphism analysis

  1. APOE gene polymorphism analysis in Barranquilla, Colombia.

    PubMed

    Ruiz, Martha; Arias, Isis; Rolón, Gloria; Hernández, Enio; Garavito, Pilar; Silvera-Redondo, Carlos

    2016-03-03

    The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.  To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.  We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.  The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.  The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

  2. Rabbit MSTN gene polymorphisms and genetic effect analysis.

    PubMed

    Qiao, X B; Xu, K Y; Li, B; Luan, X; Xia, T; Fan, X Z

    2014-04-08

    We analyzed meat samples of nine pure lines of rabbit and its 37 hybrid combinations by sequencing and single-strand conformation polymorphism techniques to explore genetic polymorphisms of all the three exon regions and part of the 5'-regulatory region of the myostatin (MSTN) gene. Thus, we detected a single nucleotide mutation (T→C) on the 476 locus of the 5'-regulatory region, but no mutation sites were detected in the exon areas. The correlation analysis showed that the mutation had some favorable genetic effects, and it resulted in increased liver weight, carcass weight, forelegs weight, back and waist weight, ham weight, and tare weight, whereas it decreased muscle drip loss and cooking loss (P < 0.05). These results suggest that the mutations in the upstream regulatory region of the MSTN gene are beneficial to the rabbit soma development, and the mutations can be used as molecular markers for the selection of the meat quality of rabbits.

  3. Polymorphism analysis of csd gene in six Apis mellifera subspecies.

    PubMed

    Wang, Zilong; Liu, Zhiyong; Wu, Xiaobo; Yan, Weiyu; Zeng, Zhijiang

    2012-03-01

    The complementary sex determination (csd) gene is the primary gene determining the gender of honey bees (Apis spp). In this study we analyzed the polymorphism of csd gene in six Apis mellifera subspecies. The genomic region 3 of csd gene in these six A. mellifera was cloned, and identified. A total of 79 haplotypes were obtained from these six subspecies. Analysis showed that region 3 of csd gene has a high level of polymorphism in all the six A. mellifera subspecies. The A. m. anatolica subspecies has a slightly higher nucleotide diversity (π) than other subspecies, while the π values showed no significant difference among the other five subspecies. The phylogenetic tree showed that all the csd haplotypes from different A. mellifera subspecies are scattered throughout the tree, without forming six different clades. Population differentiation analysis showed that there are significant genetic differentiations among some of the subspecies. The NJ phylogenetic tree showed that the A. m. caucasica and A. m. carnica have the closest relationship, followed by A. m. ssp, A. m. ligustica, A. m. carpatica and A. m. anatolica that were gathered in the tree in turn.

  4. Correlation analysis of gene polymorphisms and β-lactam allergy*

    PubMed Central

    Li, Jing; Liu, Xin-yue; Li, Lin-jing; You, Chong-ge; Shi, Lei; Zhang, Shang-di; Liu, Qian; Wang, Jun; Liu, Ze-jing; Lv, Ting-hong

    2015-01-01

    A total of 64 patients with β-lactam allergy and 30 control subjects were enrolled in a case-control study. This study is aimed to analyze the relationship between β-lactam allergy and 10 single nucleotide polymorphisms (SNPs) in interleukin-10 (IL-10), IL-13, IL-4Rα, high-affinity immunoglobulin E-receptor β chain (FcεRIβ), interferon γ receptor 2 (IFNGR2), and CYP3A4, and within the Han Chinese population of Northwest China. Genotyping for the SNPs was conducted using the Sequenom MassARRAY®platform. SPSS 17.0 was employed to analyze the statistical data and SHEsis was used to perform the haplotype reconstruction and analyze linkage disequilibrium of SNPs of IL-10 and IL-13. The results showed that the genotype distribution of CYP3A4 rs2242480/CT differed significantly between case and control groups of males (P=0.022; odds ratio (OR)=0.167, 95% confidence interval (CI): 0.032–0.867). Further analysis showed that CCA, CCG, and TAA haplotypes of IL-10 had no significant correlation in patients with β-lactam allergy. The correlation between CCT and CAC haplotypes of IL-13 and β-lactam allergy needs to be further studied. The analysis did not reveal any differences in the distribution of others gene polymorphisms between cases and controls. PMID:26160721

  5. A meta-analysis of PDE-gene polymorphism and cerebral infarction risk

    PubMed Central

    Wu, Wei-Lin; Feng, Xue-Wen; Qiu, Chen-Feng; Lin, Jing; Bao, Xian-Jun

    2017-01-01

    Previous studies identified that phosphodiesterase 4D (PDE4D) gene polymorphism might be associated with cerebral infarction or ischemic stroke, and hemorrhagic stroke in human populations. However, as yet, no meta-analysis has revealed any detailed association. We retrospectively reviewed studies regarding the relationship of PDE4D gene polymorphism with ischemic stroke (IS) published during the period January 2003 to September 2012. According to the inclusion criteria, 9 of 105 initial studies were included in the subsequent analysis. The PubMed, Embase and CNKI of China were searched to identify the relevant studies. A total of 186 young patients with IS were included for the meta-analysis and 232 matched control subjects were enrolled and results were presented. The association of PDE4D gene polymorphism with IS in various populations was examined. The results suggested that single nucleotide polymorphism (SNP), SNP 83 in PDE4D gene was significantly related with susceptibility to IS. The meta-analysis also showed that PDE4D gene was associated with an enhanced risk of IS. The meta-analysis suggested that PDE4D SNP 87 constitutes an independent risk factor for IS development. To the best of our knowledge, the present meta-analysis reveals a number of possible associations between PDE4D gene polymorphism and IS. PMID:28587358

  6. Genetic polymorphisms of interleukin genes and the risk of Alzheimer's disease: An update meta-analysis.

    PubMed

    Mun, Myung-Jin; Kim, Jin-Ho; Choi, Ji-Young; Jang, Won-Cheoul

    2016-06-01

    Recently, several meta-analyses have reported an association between interleukin (IL) gene polymorphisms and the risk of Alzheimer's disease (AD). Several further papers discussing the relationship with the risk of AD have recently been published. The aim of this meta-analysis was to re-evaluate and update the associations between IL gene polymorphisms and the risk of AD. The search sources were PubMed, Science Direct, Scopus, and Google Scholar up to July 2015, and the following search terms were used: "interleukin 1 or interleukin 6 or interleukin 10" and "variant or polymorphism or SNP" in combination with "Alzheimer's disease". A meta-analysis using the pooled odds ratios and 95% confidence intervals was carried out to assess the associations between four polymorphisms of IL genes (- 889C > T in IL-1α, - 511C > T in IL-1β, - 174G > C in IL-6 and - 1082G > A in IL-10) and the risk of AD under the heterozygous, homozygous, dominant, and recessive models with fixed- or random-effects models. A total of 21,864 cases and 40,321 controls from 93 individual studies were included in this meta-analysis. Our results indicated that the - 889C > T polymorphism was strongly associated with the increased risk of AD. However, three polymorphisms were not associated with the risk of AD. Similar to previous meta-analyses, our updated meta-analysis suggested that the - 889C > T polymorphism may be a factor in AD. However, the results of our meta-analysis of the - 174G > C polymorphism differed from those of previous meta-analyses. Consequently, we suggest that the - 174G > C polymorphism may not be a risk factor for AD.

  7. Polymorphism Interaction Analysis (PIA): a method for investigating complex gene-gene interactions

    PubMed Central

    Mechanic, Leah E; Luke, Brian T; Goodman, Julie E; Chanock, Stephen J; Harris, Curtis C

    2008-01-01

    Background The risk of common diseases is likely determined by the complex interplay between environmental and genetic factors, including single nucleotide polymorphisms (SNPs). Traditional methods of data analysis are poorly suited for detecting complex interactions due to sparseness of data in high dimensions, which often occurs when data are available for a large number of SNPs for a relatively small number of samples. Validation of associations observed using multiple methods should be implemented to minimize likelihood of false-positive associations. Moreover, high-throughput genotyping methods allow investigators to genotype thousands of SNPs at one time. Investigating associations for each individual SNP or interactions between SNPs using traditional approaches is inefficient and prone to false positives. Results We developed the Polymorphism Interaction Analysis tool (PIA version 2.0) to include different approaches for ranking and scoring SNP combinations, to account for imbalances between case and control ratios, stratify on particular factors, and examine associations of user-defined pathways (based on SNP or gene) with case status. PIA v. 2.0 detected 2-SNP interactions as the highest ranking model 77% of the time, using simulated data sets of genetic models of interaction (minor allele frequency = 0.2; heritability = 0.01; N = 1600) generated previously [Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 2007, 31:306–315.]. Interacting SNPs were detected in both balanced (20 SNPs) and imbalanced data (case:control 1:2 and 1:4, 10 SNPs) in the context of non-interacting SNPs. Conclusion PIA v. 2.0 is a useful tool for exploring gene*gene or gene*environment interactions and identifying a small number of putative associations which may be investigated further using other statistical methods

  8. RAD51 Gene 135G/C polymorphism and ovarian cancer risk: a meta-analysis.

    PubMed

    Hu, Xingzhong; Sun, Suyu

    2015-01-01

    Previous studies suggest that the RAD51 gene 135G/C polymorphism could be potentially associated with the risk of ovarian cancer. However, results from observational studies are conflicting rather than conclusive. We performed a meta-analysis of the literature aiming to clarify the relationship between the polymorphism of RAD51 gene 135G/C polymorphism and the risk of ovarian cancer. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We identified five eligible articles, 2336 ovarian cancer cases and 3548 controls. Meta-analysis results showed no significant association between 135G/C polymorphism in the RAD51 gene and ovarian cancer risk (GG vs CC: OR=0.42, 95% CI 0.16-1.06; GC vs CC: OR=0.37, 95% CI 0.12-1.16; Dominant model: OR=0.38, 95% CI 0.13-1.06; Recessive model: OR=1.20, 95% CI 0.91-1.58). No publication bias was found in the present study. This meta-analysis suggests that the RAD51 gene 135G/C polymorphism was not associated with risk of ovarian cancer. Further large and well-designed studies are needed to confirm this conclusion.

  9. Gene Polymorphisms in Chronic Periodontitis

    PubMed Central

    Laine, Marja L.; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (R)-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP. PMID:20339487

  10. The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

    PubMed

    Ren, Zheng-Ju; Ren, Peng-Wei; Yang, Bo; Liao, Jian; Liu, Sheng-Zhuo; Fang, Kun; Ren, Shang-Qing; Liu, Liang-Ren; Dong, Qiang

    2017-11-01

    To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

  11. Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals.

    PubMed

    Weng, Hong; Yan, Yan; Jin, Ying-Hui; Meng, Xiang-Yu; Mo, Yuan-Yuan; Zeng, Xian-Tao

    2016-04-20

    We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Science was conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6 polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/T polymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/T polymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis.

  12. Associations between Interleukin-1 Gene Polymorphisms and Coronary Heart Disease Risk: A Meta-Analysis

    PubMed Central

    Zhou, Liang; Cai, Jianguang; Liu, Gang; Wei, Yuan; Tang, Hui

    2012-01-01

    Objective A great number of studies regarding the associations between IL-1B-511, IL-1B+3954 and IL-1RN VNTR polymorphisms within the IL-1gene cluster and coronary heart disease (CHD) have been published. However, results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Methods Published literature from PubMed and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed- effect model. Results Thirteen studies (3,219 cases/2,445 controls) for IL-1B-511 polymorphism, nine studies (1,828 cases/1,818 controls) for IL-1B+3954 polymorphism and twelve studies (2,987 cases/ 2,208 controls) for IL-1RN VNTR polymorphism were included in this meta analysis. The results indicated that both IL-1B-511 and IL-1B+3954 polymorphisms were not associated with CHD risk (IL-1B-511 T vs. C: OR = 0.98, 95%CI 0.87–1.09; IL-1B+3954 T vs. C: OR = 1.06, 95%CI 0.95–1.19). Similarly, there was no association between IL-1RN VNTR polymorphism and CHD risk (*2 vs. L: OR = 1.00, 95%CI 0.85–1.17). Conclusions This meta-analysis suggested that there were no associations between IL-1 gene cluster polymorphisms and CHD. PMID:23029154

  13. Vitamin D receptor gene FokI polymorphisms and tuberculosis susceptibility: a meta-analysis

    PubMed Central

    Cao, Yan; Cao, Zhihong; Cheng, Xiaoxing

    2016-01-01

    Introduction The association between FokI polymorphism of vitamin D receptor (VDR) and tuberculosis (TB) susceptibility has been investigated previously; however, the results were inconsistent and conflicting. In the present study, a meta-analysis was performed to assess the relationship between VDR FokI gene polymorphism and the risk of TB. Material and methods Databases including PubMed and Embase were searched for genetic association studies of FokI polymorphism of vitamin D receptor (VDR) and TB. Data were extracted by two independent authors and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association between VDR FokI gene polymorphism and TB risk. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Results Thirty-four studies with a total of 5669 cases and 6525 controls were reviewed in the present meta-analysis. A statistically significant correlation was found between VDR FokI gene polymorphism and increased TB risk in two comparison models: the homozygote model (ff vs. FF: OR = 1.37, 95% CI: 1.17–1.60; Pheterogeneity = 0.001) and the recessive model (ff vs. Ff + FF: OR = 1.32, 95% CI: 1.14–1.52; Pheterogeneity = 0.006). Meta-regression found no source contributing to heterogeneity. However, sub-group analyses revealed that there was a statistically increased TB risk in the East and Southeast Asian population. Conclusions Synthesis of the available studies suggests that homozygosity for the FokI polymorphism of the VDR gene might be associated with an increased TB risk, especially in the East and Southeast Asian population. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed. PMID:27695504

  14. Rapid methods for population-scale analysis for gene polymorphisms: the ACE gene as an example.

    PubMed Central

    O'Dell, S. D.; Humphries, S. E.; Day, I. N.

    1995-01-01

    OBJECTIVE--To obtain rapid, high throughput genotyping of the angiotensin converting enzyme (ACE) gene intron 16 insertion/deletion polymorphism. METHODS--DNA was obtained from whole blood samples by a simple liquid phase methanol extraction procedure. The ACE gene was amplified by the polymerase chain reaction (PCR) using two oligonucleotide primers (ACE1 and ACE3) outside the insertion sequence and one primer (ACE2) inside the sequence. Microtitre array diagonal gel electrophoresis (MADGE) was used to determine genotypes. RESULTS--84 and 65 bp PCR products indicating the presence of deletion (D) and insertion (I) alleles, respectively, were clearly resolved after electrophoresis on a 7.5% polyacrylamide gel. Up to 480 DNA samples on 5 gels could be genotyped in a single electrophoresis run, or up to 1000 samples in a working day. CONCLUSIONS--A simplified DNA extraction protocol coupled to the high throughput capability of the MADGE electrophoretic system for genotyping enables analysis of large populations for association studies of ACE genotype with cardiac disease events. Images PMID:7756072

  15. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis

    PubMed Central

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    Objective: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. Methods: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. Results: The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). Conclusion: For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer. PMID:26884950

  16. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis.

    PubMed

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer.

  17. Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta-Analysis

    PubMed Central

    Ma, Wen-Qi; Han, Xi-Qiong; Wang, Xin; Wang, Ying; Zhu, Yi; Liu, Nai-Feng

    2016-01-01

    Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13–1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12–1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03–1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19–2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06–1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD

  18. Association of VEGF gene polymorphisms with diabetic retinopathy: a meta-analysis.

    PubMed

    Gong, Jian-Yang; Sun, Ye-Huan

    2013-01-01

    Studies on the association of vascular endothelial growth factor (VEGF) gene -460T/C and -2578C/A polymorphisms with diabetic retinopathy (DR) have reported conflicting results. The aim of the present study was to assess the association by using meta-analysis. A systematic search of electronic databases (PubMed, EMBASE, Elsevier Science Direct, ISI Web of Science, CBM, CNKI and VIP) was carried out until Sept 18, 2013. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. Eleven studies (-460T/C: 6 studies including 932 cases and 722 controls; -2578C/A: 6 studies including 1,071 cases and 1,137 controls) were involved in this meta-analysis. Significant association was found for -460T/C polymorphism (C versus T: OR=1.48, 95%CI=1.07-2.05, P=0.02; TC+CC versus TT: OR=1.78, 95%CI=1.02-3.12, P=0.04; CC versus TT+TC: OR=1.76, 95%CI=1.10-2.81, P=0.02), but not for -2578C/A polymorphism (P>0.05). Similar results were found in the subgroup analysis. This meta-analysis demonstrates that DR is associated with VEGF gene -460T/C polymorphism, but not -2578C/A polymorphism. Further case-control studies based on larger sample size are still needed, especially for -2578C/A polymorphism.

  19. Effect of PSCA gene polymorphisms on gastric cancer risk and survival prediction: A meta-analysis

    PubMed Central

    ZHANG, TAO; CHEN, YUAN-NENG; WANG, ZHEN; CHEN, JUN-QIANG; HUANG, SHI

    2012-01-01

    Previous studies have shown that two single-nucleotide polymorphisms (SNPs) in PSCA (rs2976392 and rs2294008) are associated with gastric cancer (GC), but the results are conflicting. Additionally, the prognostic value of PSCA gene polymorphisms for GC patients is unknown. We performed a meta-analysis using 9 eligible case-control studies to investigate the association between PSCA polymorphisms and GC risk, and additionally investigated the prognostic value of PSCA polymorphisms for GC patients with two eligible studies. The association was measured using random-effect or fixed-effect odds ratios (ORs) combined with 95% confidence intervals (CIs) according to the heterogeneity of the studies. We found that rs2294008 (dominant model: OR, 1.44; 95% CI, 1.16–1.79) and rs2976392 (dominant model: OR, 1.41; 95% CI, 0.98–2.04) polymorphisms were associated with increased risk of GC, although the association of rs2976392 was not statistically significant. For rs2294008, the associations were all consistently significant among the different subgroups stratified by ethnicity and tumor location, but not significant in intestinal or diffuse subtypes. For rs2976392, the associations were consistently significant for the intestinal, diffuse and non-cardia subtypes, but not significant for the cardia subtype. Furthermore, two eligible studies reported inverse results of PCSA in predicting the survival of GC patients (HR, 0.75; 95% CI, 0.59–0.96; and HR, 2.12; 95% CI, 1.22–3.69, respectively). In conclusion, PSCA gene polymorphisms are associated with increased risk of GC and are correlated with the prognosis of GC patients. Future studies are required to evaluate the molecular mechanisms of PSCA polymorphisms in GC and validate the prognostic value in a larger number of patients. PMID:23060941

  20. Interleukin-10 gene polymorphisms and hepatocellular carcinoma susceptibility: A meta-analysis

    PubMed Central

    Wei, Yong-Gang; Liu, Fei; Li, Bo; Chen, Xi; Ma, Yu; Yan, Lv-Nan; Wen, Tian-Fu; Xu, Ming-Qing; Wang, Wen-Tao; Yang, Jia-Yin

    2011-01-01

    AIM: To assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility. METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. RESULTS: This meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identified as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32). CONCLUSION: This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC. PMID:22025883

  1. In silico analysis of polymorphisms in microRNAs that target genes affecting aerobic glycolysis

    PubMed Central

    Venkatesh, Thejaswini; Tsutsumi, Rie

    2016-01-01

    Background Cancer cells preferentially metabolize glucose through aerobic glycolysis, an observation known as the Warburg effect. Recently, studies have deciphered the role of oncogenes and tumor suppressor genes in regulating the Warburg effect. Furthermore, mutations in glycolytic enzymes identified in various cancers highlight the importance of the Warburg effect at the molecular and cellular level. MicroRNAs (miRNAs) are non-coding RNAs that posttranscriptionally regulate gene expression and are dysregulated in the pathogenesis of various types of human cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect miRNA biogenesis, processing, function, and stability and provide additional complexity in the pathogenesis of cancer. Moreover, mutations in miRNA target sequences in target mRNAs can affect expression. Methods In silico analysis and cataloguing polymorphisms in miRNA genes that target genes directly or indirectly controlling aerobic glycolysis was carried out using different publically available databases. Results miRNA SNP2.0 database revealed several SNPs in miR-126 and miR-25 in the upstream and downstream pre-miRNA flanking regions respectively should be inserted after flanking regions and miR-504 and miR-451 had the fewest. These miRNAs target genes that control aerobic glycolysis indirectly. SNPs in premiRNA genes were found in miR-96, miR-155, miR-25 and miR34a by miRNASNP. Dragon database of polymorphic regulation of miRNA genes (dPORE-miRNA) database revealed several SNPs that modify transcription factor binding sites (TFBS) or creating new TFBS in promoter regions of selected miRNA genes as analyzed by dPORE-miRNA. Conclusions Our results raise the possibility that integration of SNP analysis in miRNA genes with studies of metabolic adaptations in cancer cells could provide greater understanding of oncogenic mechanisms. PMID:27004216

  2. Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis.

    PubMed

    Liao, Xiaoyang; Yang, Zhiyi; Peng, Daqing; Dai, Hua; Lei, Yi; Zhao, Qian; Han, Yanbing; Wang, Weiwen

    2014-09-01

    The association between T174M polymorphism of angiotensinogen gene and essential hypertension risk remains controversial. We herein performed a meta-analysis to achieve a reliable estimation of their relationship. All the studies published up to May 2013 on the association between T174M polymorphism and essential hypertension risk were identified by searching the electronic repositories PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Ultimately, nine eligible studies, including 2188 essential hypertension cases and 2459 controls, were enrolled in this meta-analysis. No significant associations were found under the overall ORs for M-allele comparison (M vs. T, pooled OR 0.92, 95% CI 0.62-1.37), MM vs. TT (pooled OR 0.86, 95% CI 0.29-2.51), TM vs. TT n (pooled OR 0.91, 95% CI 0.63-1.32), recessive model (MM vs. TT+TM, pooled OR 0.89, 95% CI 0.35-2.30), dominant model (MM+TM vs. TT, pooled OR 0.91, 95% CI 0.60-1.38) between T174M polymorphism and risk for essential hypertension. This meta-analysis suggested that the T174M polymorphism of the angiotensinogen gene might not be associated with the susceptibility of essential hypertension in Asian or European populations.

  3. DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.

    PubMed

    Flores-Martínez, S E; Islas-Andrade, S; Machorro-Lazo, M V; Revilla, M C; Juárez, R E; Mújica-López, K I; Morán-Moguel, M C; López-Cardona, M G; Sánchez-Corona, J

    2004-01-01

    Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed. We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

  4. Analysis of DRB3 gene polymorphisms in Jafarabadi, Mediterranean, and Murrah buffaloes from Brazil.

    PubMed

    Stafuzza, N B; Olivatto, L M; Naressi, B C M; Tonhati, H; Amaral-Trusty, M E J

    2016-03-31

    The DRB3 gene is an MHC class II gene that has a high degree of polymorphism with more than 100 alleles described in cattle. This variation contributes to differences among individuals in immune responsiveness and disease resistance. In this study, we searched for allelic variants in exon 2 of the DRB3 gene in 80 river buffaloes of three breeds in Brazil using a PCR-RFLP technique. The PCR product showed genetic polymorphism when digested with RsaI, PstI or HaeIII restriction enzymes. In total, 16 restriction patterns were identified: nine restriction patterns and 16 genotypes were found with RsaI; four restriction patterns and nine genotypes were found with HaeIII; and, three restriction patterns and four genotypes were found with PstI. Three RFLP patterns were exclusive to Jafarabadi buffaloes (RsaI-b, RsaI-c and RsaI-f) and three others were only observed in Mediterranean buffaloes (RsaI-g, RsaI-h and PstI-y). Jafarabadi buffaloes had a larger number of RFLP patterns than Mediterranean and Murrah breeds. The analysis showed that the DRB3 exon 2 was highly polymorphic, with the highest degree of polymorphism in Mediterranean buffaloes. This study provides the first assessment of allelic variation among three different buffalo breeds from Brazil and provides a basis for further investigations into the association between the DRB3 alleles and disease resistance.

  5. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: a meta-analysis.

    PubMed

    Li, Pingping; Qin, Chao

    2014-02-10

    Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case-control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I(2) and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI): 1.17-1.40, P<0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke. © 2013.

  6. Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

    PubMed

    Fu, Jie; Wang, Jingqiu; Luo, Yanping; Zhang, Lifeng; Zhang, Yuan; Dong, Xinfang; Yu, Hongjuan; Cao, Mingqiang; Ma, Xingming

    2016-11-01

    The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Analysis of gene-derived SNP marker polymorphism in wheat (Triticum aestivum L.)

    USDA-ARS?s Scientific Manuscript database

    In this study, we analyzed 359 single nucleotide polymorphisms (SNPs) previously discovered in intron sequences of wheat genes to evaluate SNP marker polymorphism in common wheat (Triticum aestivum L.). These SNPs showed an average polymorphism information content (PIC) of 0.181 among 20 US wheat c...

  8. Analysis of cytokine gene polymorphisms in Mestizo and native populations from Mexico.

    PubMed

    Mendoza-Carrera, Francisco; Castro-Martínez, Xochitl Helga; Leal, Caridad; Portilla-de Buen, Eliseo; Sánchez-Corona, José; Flores-Martínez, Silvia Esperanza; García-Zapién, Alejandra; Ramírez-López, Guadalupe; Gómez-Espinel, Irene; Báez-Duarte, Blanca Guadalupe; Zamora-Ginez, Irma; Velarde-Félix, Jesús Salvador; Guillermo Sánchez-Zazueta, Jorge

    2017-01-01

    To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians - an Amerindian group from southeastern Mexico - were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F-statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country. © 2016 Wiley Periodicals, Inc.

  9. Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

    PubMed

    Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

    2014-01-01

    Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

  10. New insights in HLA-E polymorphism by refined analysis of the full-length gene.

    PubMed

    Olieslagers, T I; Voorter, C E M; Groeneweg, M; Xu, Y; Wieten, L; Tilanus, M G J

    2017-03-01

    Human leukocyte antigen (HLA)-E is a non-classical HLA class I molecule that plays a role in both the innate and the adaptive immune response through interaction with receptors on natural killer- and T-cells. The HLA-E gene is characterized by limited polymorphism compared with the classical HLA loci on chromosome 6. At the start of this study, only 13 variable sites had been identified (IPD-IMGT/HLA Database v3.18.0). While most previous studies focused on polymorphism in exons 2 and 3 or specific gene regions, polymorphism in the other exons and introns could influence protein expression and function as well. Studies that investigate extended HLA-E polymorphism are therefore needed to better understand the functional relevance of HLA-E in health and disease. The aim of this study was to examine the variability of the full-length HLA-E gene region in individuals originating from different populations. A total of 7 new HLA-E alleles were identified using full-length HLA-E sequencing of 123 individuals from Asian, Dutch or Hunan Han origin. Furthermore, genome variation analysis of the third phase of the 1000 genomes database showed 107 new variable sites in 2504 individuals originating from 26 different populations. Our study demonstrates that the nucleotide variability of the HLA-E gene is much higher than previously known, albeit in only a limited number of individuals. Overall only 2 variants, HLA-E*01:01 and *01:03, are frequently present worldwide, suggesting that balancing selection is acting on HLA-E. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Interleukin-6 gene -174G/C polymorphism and bronchial asthma risk: a meta-analysis

    PubMed Central

    Li, Fangwei; Xie, Xinming; Li, Shaojun; Ke, Rui; Zhu, Bo; Yang, Lan; Li, Manxiang

    2015-01-01

    The Interleukin-6 (IL-6) genetic polymorphism is associated with bronchial asthma, a number of studies have been conducted to investigate the association between IL-6 gene -174G/C polymorphism and bronchial asthma risk. However, the results are inconclusive. This meta-analysis aims to investigate whether -174G/C polymorphism is a potential risk factor for bronchial asthma. We searched Web of Science, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI) and Wanfang Database from inception through December 1st, 2014. Meta-analysis was performed using the STATA 12.0. Overall, a significantly reduced risk for asthma was found in IL-6 -174 CC genotype (CC vs. GG: OR = 0. 51, 95% CI = 0.27-0.96, P = 0.038). Furthermore, analysis by ethnicity indicated that there was a markedly reduced risk for asthma in IL-6 -174 CC genotype in Caucasian (CC vs. GG: OR = 0.51, 95% CI = 0.27-0.96, P = 0.038). Analysis by age indicated that there was a significantly reduced risk for asthma in IL-6 -174 CC genotype in adults (CC vs. GG: OR = 0.47, 95% CI = 0.23-0.97, P = 0.042). In conclusion, the current meta-analysis indicates that IL-6 -174 CC genotype may be a protective factor against asthma in Caucasian and adults. PMID:26550171

  12. Analysis of Association Between MGMT and p53 Gene Single Nucleotide Polymorphisms and Laryngeal Cancer.

    PubMed

    Lv, Yayun; Jia, Chuanliang; Jiang, Aihua; Zhang, Hua; Wang, Yunqiang; Liu, Feifei; Yang, Linlin; Sun, Yan; Lv, Runli; Song, Xicheng

    2017-08-01

    To investigate the p53 and O(6)-methylguanine DNA methyltransferase (MGMT)5' upstream sequence gene promoter regions for single nucleotide polymorphisms and explore the p53 gene 5' upstream sequence consisting of two haplotypes to provide a genetic marker for the incidence of laryngeal squamous cell carcinoma. We included 96 cases of laryngeal squamous cell carcinoma and 102 controls. We used SNaPshot micro-sequencing analysis of the MGMT promoter region for four single nucleotide polymorphisms and p53 gene 5' upstream sequence loci (rs1625649, rs2287499, rs2287498, rs228749) genotypes. We calculated and compared two groups for genotypic and allelic frequencies, applied HaploView4.2 for computing rs2287499, rs2287498, rs228749 values and haplotype frequencies and tested control loci and Hardy-Weinberg equilibrium. All the experimental data were statistically evaluated using SPSS17.0. The Chi-square test was used for statistical analysis with p<0.05 indicating statistical significance. 5'Upstream single nucleotide polymorphisms rs1625649, rs2287499, rs2287498, rs228749 of p53 were polymorphic in both patient and control groups. There was no statistical significance in frequency distributions for the four loci genotypes when comparing patients and healthy controls (Chi-square values were 4.47, 0.98, 1.67, 4.68, respectively; p>0.05). However, allelic frequencies of the MGMT promoter region locus rs1625649 between patients and healthy control groups were statistically significantly different (chi-square value of 5.77; p<0.05). Differences between allelic frequencies for the p53 gene 5' upstream sequence loci rs2287499, rs2287498 and rs228749 between patients and the healthy control group were not statistically significant (Chi-square values were 1.11,1.56,3.36; p>0.05). Nor were those for the two haplotypes of rs2287499, rs2287498 and rs228749 between patients and the healthy control group were not statistically significant (Chi-square value 1.46, p>0.05). MGMT gene

  13. Polymorphism analysis and new JAG1 gene mutations of Alagille syndrome in Mexican population☆

    PubMed Central

    Vázquez-Martínez, Edgar Ricardo; Varela-Fascinetto, Gustavo; García-Delgado, Constanza; Rodríguez-Espino, Benjamín Antonio; Sánchez-Boiso, Adriana; Valencia-Mayoral, Pedro; Heller-Rosseau, Solange; Pelcastre-Luna, Erika Lisselly; Zenteno, Juan C.; Cerbón, Marco; Morán-Barroso, Verónica Fabiola

    2013-01-01

    Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20–89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population. PMID:25606387

  14. Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis.

    PubMed

    Kumar, Amit; Kumar, Pradeep; Prasad, Manya; Sagar, Ram; Yadav, Arun Kumar; Pandit, Awadh Kishor; Jali, Vidishaa Prasad; Pathak, Abhishek

    2015-07-01

    Studies on association between methylenetetrahydrofolate reductase gene (MTHFR) C677T gene polymorphism and ischemic stroke have shown conflicting results. We have conducted a meta-analysis to determine the precise association of the C677T polymorphism of MTHFR gene with risk of ischemic stroke. We searched electronic databases Medline, EMBASE, and Google Scholar (last search dated till August 2014). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from random or fixed-effects models were calculated. The methodological quality of included studies was determined by the quality assessment scale. Thirty eight case-control studies fulfilled our inclusion criteria comprising 6310 patients and 8297 controls. The significant associations between MTHFR C677T genetic polymorphism and risk of ischemic stroke were observed in dominant (OR, 1·09; 95% CI, 1·06-1·12, P-value < 0·001) and recessive (OR, 1·31; 95% CI, 1·19-1·44, P-value < 0·001) inheritance models. In an Asian population, significant association between the MTHFR polymorphism and ischemic stroke was observed (dominant model: OR 1·36, 95% CI 1·23-1·49 and under recessive model OR, 1·29; 95% CI, 1·15-1·45). In the Caucasian population borderline, non-significant association was observed under dominant model of inheritance (OR, 1·05; 95% CI, 0·99-1·10) but significant association was observed under the recessive model of inheritance (OR, 1·33; 95% CI, 1·13-1·58). The present study results suggest that MTHFR C677T genetic polymorphism is a probable risk of ischemic stroke.

  15. Association of insulin degrading enzyme gene polymorphisms with Alzheimer's disease: a meta-analysis.

    PubMed

    Cheng, Huawei; Wang, Lin; Shi, Tianlu; Shang, Yuping; Jiang, Ling

    2015-05-01

    Alzheimer's disease (AD) is a chronic degenerative disorder. It is caused by both genetic and environmental factors. The association of Insulin Degrading Enzyme (IDE) genotypes rs4646953, rs2251101 and rs1544210 with AD has been detected, but the findings were conflicted, however, Apolipoprotein-E (APOE)-ε4 allele has been observed as a genetic risk factor for AD. To investigate the issue, a meta-analysis was performed. We searched PubMed, Springer Link, AlzGene and CNKI for relevant literatures published by June 2013. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to explore the significant association. A total of 11 studies comprising 5771 cases and 5474 controls were considered in final meta-analysis. We found that weak connections existed between rs4646953 (TT vs. CC: z = 2.24, p = 0.025, OR = 1.536) and AD, but no significant associations have been found between other IDE gene single nucleotide polymorphisms of rs4646953, rs2251101 and rs1544210 with AD. We certified that APOE-ε4 allele was still be a suspected factor to AD. There was no evidence for obvious publication bias in overall meta-analysis. Furthermore, larger-scale randomized controlled trials are necessary to validate the association between IDE gene polymorphisms with AD.

  16. Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis.

    PubMed

    Xu, Jie; Jin, Jun; Tan, Sheng

    2016-05-01

    Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings. © 2016 John Wiley & Sons Ltd/University College London.

  17. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  18. Association Between Interleukin-6 Gene Polymorphisms and Bone Mineral Density: A Meta-Analysis

    PubMed Central

    Wang, Zhao; Yang, Yonghong; He, Minjuan; Wang, Ran; Ma, Juming; Zhang, Yimin; Zhao, Lingyun

    2013-01-01

    Background: Many studies have examined the association between interleukin-6 (IL-6) gene polymorphisms and bone mineral density (BMD). However, the results remain conflicting. To assess the relationship more precisely, a meta-analysis was performed. Methods: The PubMed, Embase, Chinese BioMedical Literature (CBM), Wanfang, and China National Knowledge Infrastructure (CNKI) database were searched for relevant articles published up to March 2013. Weighted mean difference (WMD) and 95% confidence interval (95% CI) were calculated using a fixed-effects or random-effects model. Results: A total of 16 articles with 11,957 subjects were investigated in this meta-analysis. Overall, −634C/G polymorphism was significantly associated with BMD at the femoral neck (WMD, −0.016 g/cm2; 95% CI, −0.028 to −0.003 g/cm2), lumbar spine (WMD, −0.049 g/cm2; 95% CI, −0.069 to −0.030 g/cm2), and whole body (WMD, −0.023 g/cm2; 95% CI, −0.037 to −0.009 g/cm2) for GG versus CC+CG. In subgroup analyses stratified by ethnicity, individuals carrying −634GG genotype had a significantly lower mean BMD at any skeletal site examined, compared with individuals with −634CC or −634CG genotype in Asian populations. For −174G/C polymorphism, the BMD differences between CC+CG and GG genotype were 0.004 g/cm2 at the distal radius (95% CI, 0.004 to 0.005 g/cm2), 0.011 g/cm2 at the trochanter (95% CI, 0.002 to 0.020 g/cm2), and 0.017 g/cm2 at the Ward's triangle (95% CI, 0.003 to 0.032 g/cm2). No significant publication bias was observed in either the −634C/G or −174G/C polymorphism. Conclusions: This suggests that there are modest effects of the −634C/G and −174G/C polymorphisms on BMD. Large-scale and well-designed studies are required to further investigate gene–gene and gene–environment interactions on IL-6 polymorphisms and BMD in various populations. PMID:24053561

  19. Association between BHMT gene rs3733890 polymorphism and cancer risk: evidence from a meta-analysis

    PubMed Central

    Xu, Yue; Yan, Cunye; Hao, Zongyao; Zhou, Jun; Fan, Song; Tai, Sheng; Yang, Cheng; Zhang, Li; Liang, Chaozhao

    2016-01-01

    Background and objective The gene betaine-homocysteine methyltransferase (BHMT) has drawn much attention during the past decades. An increasing number of clinical and genetic investigations have supposed that BHMT rs3733890 polymorphism might be associated with risk of breast cancer and ovarian cancer. As no consistent conclusion has been achieved, we conducted an up-to-date summary of BHMT rs3733890 polymorphism and cancer risk through a meta-analysis. Materials and methods The articles were collected from PubMed, Google Scholar, and CNKI (Chinese) databases up to December 2015. Then, the correlations were determined by reading the titles and abstracts and by further reading the full text to filter the unqualified articles. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) were used to assess the results. Results Among 187 articles collected in the analysis, seven studies with a total of 2,832 cases and 3,958 controls were included for evaluation of the association between BHMT rs3733890 polymorphism and susceptibility of cancer risk. The heterogeneity test showed no significant differences. Furthermore, we found that BHMT −742G>A polymorphism in case and control groups showed no statistically significant association with susceptibility in various cancer types except for uterine cervical cancer (A vs G: OR =0.641, 95% CI =0.445–0.923, P=0.017; AA+AG vs GG: OR =0.579, 95% CI =0.362–0.924, P=0.022). In addition, no statistically significant association was uncovered when stratification analyses were conducted by ethnicity and genotyping methods. Conclusion Our results have shown no obvious evidence that rs3733890 polymorphism in BHMT gene affected the susceptibility of head and neck squamous cell carcinoma, breast cancer, ovarian cancer, colorectal adenoma, and liver cancer. In contrast, we found the protective role of BHMT −742G>A polymorphism in uterine cervical cancer incidence. Future well-designed studies comprising larger sample size

  20. Angiotensin-converting enzyme gene polymorphisms and risk for sporadic Alzheimer's disease: a meta-analysis.

    PubMed

    Wang, Xue-Bin; Cui, Ning-Hua; Gao, Jia-Jia; Qiu, Xue-Ping; Yang, Na; Zheng, Fang

    2015-02-01

    Numerous studies have tested for associations between common polymorphisms of the angiotensin-converting enzyme gene and sporadic Alzheimer disease (SAD), but results have been inconclusive. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms (rs4291, rs4343, rs1800764) for developing SAD. Through searching of Pubmed, Embase, Alzgene and manually searching relevant references, a total of 14 articles with 26 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. The heterogeneity across the studies was tested, as was publication bias. We observed significant association between SNP rs4291 and SAD using allelic comparison (OR = 1.08, 95% CI 1.03-1.14), homozygote comparison (OR = 1.16, 95% CI 1.04-1.30) and the recessive model (OR = 1.10, 95% CI 1.02-1.18). Association with SNP rs1800764 was revealed but it was not sufficiently robust to withstand the Benjamini-Hochberg method and stepdown Bonferroni correction. Significant association was not identified in the analysis for SNP rs4343. In subgroup analyses, the risk of SAD associated with SNP rs4291 appeared to be significant among Caucasians and in older cases (mean age ≥75 years). Our results confirmed a significant but modest association between SNP rs4291 and SAD susceptibility. Further study of the pathogenetic characteristics of this polymorphism and independent confirmation of the association in larger studies are warranted.

  1. Association analysis of peroxisome proliferator-activated receptors gamma gene polymorphisms with asprin hypersensitivity in asthmatics

    PubMed Central

    Oh, Sun-Hee; Park, Se-Min; Park, Jong-Sook; Jang, An-Soo; Lee, Yong-Mok; Uh, Soo-Taek; Kim, Young Hoon; Choi, In-Seon; Kim, Mi-Kyeong; Park, Byeong Lae

    2009-01-01

    Purpose Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARγ regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. Methods Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). Results Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). Conclusions The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma. PMID:20224667

  2. Mutation screening in the human epsilon-globin gene using single-strand conformation polymorphism analysis.

    PubMed

    Papachatzopoulou, Adamantia; Menounos, Panagiotis G; Kolonelou, Christina; Patrinos, George P

    2006-02-01

    The human epsilon-globin gene is necessary for primitive human erythropoiesis in the yolk sac. Herein we report a non-radioactive single-strand conformation polymorphism (SSCP) approach to screen the human epsilon-globin gene and its regulatory regions for possible mutations and single-nucleotide polymorphisms in normal adult subjects, in order to determine those genomic regions, which are not necessary for its proper regulation and function. We identified no sequence variations apart from the expected 5'epsilon /HincII polymorphism in the fragments analyzed, suggesting that genomic alterations in the epsilon-globin gene are most likely incompatible with normal erythropoiesis and proper embryonic development.

  3. Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

    PubMed Central

    Diaz-Gallo, LM; Gourh, P; Broen, J; Simeon, C; Fonollosa, V; Ortego-Centeno, N; Agarwal, S; Vonk, MC; Coenen, M; Riemekasten, G; Hunzelmann, N; Hesselstrand, R; Tan, FK; Reveille, JD; Assassi, S; García-Hernandez, FJ; Carreira, P; Camps, MT; Fernandez-Nebro, A; de la Peña, P Garcia; Nearney, T; Hilda, D; González-Gay, MA; Airo, P; Beretta, L; Scorza, R; Herrick, A; Worthington, J; Pros, A; Gómez-Gracia, I; Trapiella, L; Espinosa, G; Castellvi, I; Witte, T; de Keyser, F; Vanthuyne, M; Mayes, MD; Radstake, TRDJ; Arnett, FC; Martin, J; Rueda, B

    2011-01-01

    Objective Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (pFDRcorrected=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (pFDRcorrected=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (pFDRcorrected=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases. PMID:21131644

  4. Polymorphism in IGFBP3 gene is associated with prostate cancer risk: an updated meta-analysis

    PubMed Central

    Qie, Yunkai; Nian, Xuewu; Liu, Xuesen; Hu, Hailong; Zhang, Changwen; Xie, Linguo; Han, Ruifa; Wu, Changli; Xu, Yong

    2016-01-01

    Objective Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism. Methods A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case–control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Results Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA − OR =1.16, 95% CI: 1.08–1.25) and in recessive model (CC vs AA+AC − OR =1.11, 95% CI: 1.04–1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA − OR =1.11, 95% CI: 1.05–1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05–1.14). Further stratification analysis revealed that the association between –202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02–1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model. Conclusion Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa. PMID:27462171

  5. The association between brain-derived neurotrophic factor gene polymorphism and migraine: a meta-analysis.

    PubMed

    Cai, Xiaoying; Shi, Xiaolei; Zhang, Ximeng; Zhang, Aiwu; Zheng, Minying; Fang, Yannan

    2017-12-01

    Migraine is a recurrent headache disease related to genetic variants. The brain-derived neurotrophic factor (BDNF) gene rs6265 (Val66Met) and rs2049046 polymorphism has been found to be associated with migraine. However, their roles in this disorder are not well established. Then we conduct this meta-analysis to address this issue. PubMed, Web of Science and Cochrane databases were systematically searched to identify all relevant studies. Odds ratio (OR) with corresponding 95% confidence interval (CI) was used to estimate the strength of association between BDNF gene rs6265 and rs2049046 polymorphism and migraine. Four studies with 1598 cases and 1585 controls, fulfilling the inclusion criteria were included in our meta-analysis. Overall data showed significant association between rs6265 polymorphism and migraine in allele model (OR = 0.86, 95%CI: 0.76-0.99, p = 0.03), recessive model (OR = 0.84, 95%CI: 0.72-0.98, p = 0.03) and additive model (GG vs GA: OR = 0.85, 95%CI: 0.72-1.00, p = 0.04), respectively. We also found significant association between rs2049046(A/T) polymorphism and migraine in allele model (OR = 0.88, 95%CI: 0.79-0.98, p = 0.02), recessive model (OR = 0.80, 95%CI: 0.67-0.96, p = 0.02) and additive model (AA vs TT: OR = 0.72, 95%CI: 0.57-0.92, p = 0.008; AA vs AT: OR = 0.81, 95%CI: 0.67-0.99, p = 0.03), respectively. Our meta-analysis suggested that BDNF rs6265 and rs2049046 polymorphism were associated with common migraine in Caucasian population. Further studies are awaited to update this finding in Asian population and other types of migraine.

  6. Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis.

    PubMed

    Huang, Christine H; Santangelo, Susan L

    2008-09-05

    The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism. Prior association studies of autism have yielded conflicting results regarding the association between two common 5-HTT polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR). We conducted a systematic review and meta-analysis to test the following hypotheses: (i) there is an association between autism and either or both of the 5-HTTLPR and STin2 VNTR polymorphisms, and (ii) the S allele of 5-HTTLPR and/or the STin2.12 allele of the VNTR are the specific risk alleles for autism. All published family-based and population based studies were examined to determine the overall strength of association between 5-HTT polymorphisms and autism. After exclusion of studies with overlapping samples and studies whose data did not allow for calculation of an odds ratio, 16 studies were included for final analyses, all but two of which used a family-based design. The meta-analysis failed to find a significant overall association between either of the 5-HTT polymorphisms examined and autism. Further, no allelic transmission distortion was found when studies of simplex (11 studies) and multiplex (3 studies) family samples were analyzed separately. However, there was significant heterogeneity by ethnicity; family based studies of US mixed population samples showed preferential transmission of the S allele of 5-HTTLPR (S allele:L allele = 247:183), while there was no allelic distortion among the family-based studies of European and Asian samples.

  7. Variants in multiple genes polymorphism association analysis of COPD in the Chinese Li population

    PubMed Central

    Ding, Yipeng; Yang, Danlei; Zhou, Long; Xu, Junxu; Chen, Yu; He, Ping; Yao, Jinjian; Chen, Jiannan; Niu, Huan; Sun, Pei; Jin, Tianbo

    2015-01-01

    Background It is known that the contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations. Further, previous studies involving various ethnic groups have revealed associations between COPD and genetic polymorphisms in families with sequence similarity 13, member A (FAM13A), micro-RNA 2054 (MIR2054), SET domain containing protein 7 (SETD7), ring finger protein 150 (RNF150), hedgehog interacting protein (HHIP), and vascular endothelial growth factor A (VEGFA). Our objective was to explore the association between these gene polymorphism and COPD in members of Chinese Li minority population. Materials and methods The Chinese Li population case–control study was conducted to assess genetic associations with COPD risk. Seven single nucleotide polymorphisms (SNPs) located on chromosome 4, including FAM13A, MIR2054, SETD7, RNF150, and HHIP, and nine SNPs in the VEGFA gene were genotyped among 234 cases and 240 controls using Sequenom Mass-ARRAY® platform. Linkage disequilibrium (LD) analysis was performed using Haploview software and the associations of the SNP frequencies with COPD were analyzed using chi-square (χ2) tests, genetic models analysis, and haplotype analysis. Results By χ2 we found the minor allele “G” of rs17050782 was with increased COPD risk in allele model. In genetic models, we found the minor allele of rs7671167 (P=0.028 by dominant model) and rs17050782 (P=0.008 by recessive model) was associated with the increased risk of COPD disease. Likewise, an increased risk of developing COPD was associated with the “GGCGC” haplotype of VEGFA (odds ratio =1.48, 95% confidence interval =1.02–2.12, P=0.037). Conclusion Our results were the first time to reveal that SNPs from FAM13A (rs7671167), SETD7 (rs17050782), and a haplotype of VEGFA (“GGCGC”) are potential susceptibility loci associated with increased COPD risk in Chinese Li minority population. PMID:26251585

  8. Single-nucleotide polymorphism analysis of GH, GHR, and IGF-1 genes in minipigs.

    PubMed

    Tian, Y G; Yue, M; Gu, Y; Gu, W W; Wang, Y J

    2014-09-01

    Tibetan (TB) and Bama (BM) miniature pigs are two popular pig breeds that are used as experimental animals in China due to their small body size. Here, we analyzed single-nucleotide polymorphisms (SNPs) in gene fragments that are closely related to growth traits [growth hormone (GH), growth hormone receptor (GHR), and insulin-like growth factor (IGF)-1)] in these pig breeds and a large white (LW) control pig breed. On the basis of the analysis of 100 BMs, 108 TBs, and 50 LWs, the polymorphic distribution levels of GH, GHR, and IGF-1 were significantly different among these three pig breeds. According to correlation analyses between SNPs and five growth traits--body weight (BW), body length (BL), withers height (WH), chest circumference (CC), and abdomen circumference (AC)--three SNP loci in BMs and four SNP loci in TBs significantly affected growth traits. Three SNP sites in BMs and four SNP sites in TBs significantly affected growth traits. SNPs located in the GH gene fragment significantly affected BL and CC at locus 12 and BL at locus 45 in BMs, and also BW, WH, CC, and AC at locus 45 and WH and CC at locus 93 in TBs. One SNP at locus 85 in the BM GHR gene fragment significantly affected all growth traits. All indices were significantly reduced with a mixture of alleles at locus 85. These results provide more information regarding the genetic background of these minipig species and indicate useful selection markers for pig breeding programs.

  9. Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis

    PubMed Central

    Fan, Weina; Qu, Xiaowei; Li, Jing; Wang, Xingning; Bai, Yanping; Cao, Qingmei; Ma, Liqun; Zhou, Xiaoyao; Zhu, Wei; Liu, Wei; Ma, Qiang

    2017-01-01

    ADIPOQ gene polymorphisms have been indicated to be associated with hypertension; however, published studies have reported inconsistent results. Eligible studies were retrieved by searching the PubMed, Embase and China National Knowledge Infrastructure databases. The case group consisted of patients with hypertension, and the control group consisted of subjects with normal blood pressure. Based on eleven published articles, involving 4837 cases and 5618 controls, the pooled results from rs2241766 polymorphism showed increased risk in the allelic model (G VS T: OR = 1.16, 95%CI = 1.06–1.27), recessive model (GG VS GT + TT: OR = 1.34, 95%CI = 1.10–1.63), dominant model (GG + GT VS TT: OR = 1.15, 95%CI = 1.02–1.30) and homozygote model (GG VS TT: OR = 1.38, 95%CI = 1.21–1.69). In addition, rs266729 polymorphism showed increased risk for hypertension in the recessive model (GG VS GC + CC: OR = 1.43, 95%CI = 1.02–2.01). In the Caucasian subgroup, rs1501299 polymorphism showed decreased risk of hypertension in the allelic model (T VS G: OR = 0.75, 95%CI = 0.58–0.97), dominant model (TT + TG VS GG: OR = 0.83, 95%CI = 0.71–0.98) and heterozygote model (TG VS GG: OR = 0.82, 95%CI = 0.68–0.99). The rs2241766 polymorphism was associated with a significant increase in hypertension risk based on our analysis. Moreover, an increased risk of rs266729 in hypertension patients was also detected. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in hypertension in Caucasian subgroup; however, this finding requires further study. PMID:28181566

  10. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk.

    PubMed

    Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Cunningham, Julie M; Phelan, Catherine M; Anderson, Stephanie; Rider, David N; White, Kristin L; Pankratz, V Shane; Song, Honglin; Hogdall, Estrid; Kjaer, Susanne K; Whittemore, Alice S; DiCioccio, Richard; Ramus, Susan J; Gayther, Simon A; Schildkraut, Joellen M; Pharaoh, Paul P D; Sellers, Thomas A

    2009-03-01

    Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from existing genotype data, we conducted a combined analysis of five independent studies of invasive epithelial ovarian cancer. Up to 2,120 cases and 3,382 controls were genotyped in the course of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B). Because of the semi-overlapping nature of the 123 assayed tagging SNPs, we performed multiple imputation based on fastPHASE using data from White non-Hispanic study participants and participants in the international HapMap Consortium and National Institute of Environmental Health Sciences SNPs Program. Logistic regression assuming a log-additive model was done on combined and imputed data. We observed strengthened signals in imputation-based analyses at several SNPs, particularly CDKN2A-CDKN2B rs3731239; CCND1 rs602652, rs3212879, rs649392, and rs3212891; CDK2 rs2069391, rs2069414, and rs17528736; and CCNE1 rs3218036. These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls.

  11. Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a meta-analysis.

    PubMed

    Mao, Song; Huang, Songming

    2014-03-01

    To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the risk of rickets among Asians. Eligible studies were included in our meta-analysis by searching PubMed, Embase, Cochrane and China National Knowledge Infrastructure databases according to a predefined criteria. A random effects model was used to calculate the combined ORs and its corresponding 95% CI. 16 studies were recruited for the analysis of the association between VDR BsmI (rs1544410), TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) gene polymorphisms and the risk of rickets among Asians, most of whom were from China. B allele/BB genotype was associated with the susceptibility of rickets (p=0.017 and 0.044, respectively), and bb genotype was associated with lower risk of rickets (p=0.033). F allele/FF genotype was associated with the susceptibility of rickets (p<10(-4)), and ff genotype was associated with lower risk of rickets (p<10(-4)). AA genotype was associated with the onset of rickets (p=0.044). No significant association was observed between TaqI polymorphism the risk of rickets. A allele/aa genotype was not associated with the risk of rickets. No evidence of publication bias was observed. B allele/BB genotype at the BsmI site, F allele/FF genotype at the FokI site and AA genotype at the ApaI site may be risk factors for the onset of rickets among Asians; bb genotype at the BsmI site and ff genotype at the FokI site may be protective factors against the risk of rickets among Asians.

  12. Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

    PubMed

    Shawkatová, Ivana; Javor, Juraj; Párnická, Zuzana; Bucová, Mária; Čopíková-Cudráková, Daniela; Michalík, Jozef; Gmitterová, Karin; Čierny, Daniel; Buc, Milan; Ďurmanová, Vladimíra

    2017-01-27

    Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.

  13. DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.

    PubMed

    Peng, Qiliu; Mo, Cuiju; Tang, Weizhong; Chen, Zhiping; Li, Ruolin; Zhai, Limin; Yang, Shi; Wu, Junrong; Sui, Jingzhe; Li, Shan; Qin, Xue

    2014-03-01

    The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 16 case-control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR = 1.174, 95%CI = 1.033-1.335, P = 0.014 and recessive model TT vs. TC + CC: OR = 1.147, 95%CI = 1.020-1.290, P = 0.022, respectively). The results were still significant after excluding the Hardy-Weinberg equilibrium violation studies (TT vs. CC: OR = 1.178, 95%CI = 1.036-1.339, P = 0.013 and recessive model TT vs. TC + CC: OR = 1.144, 95%CI = 1.017-1.287, P = 0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT + TC vs. CC: OR = 1.285, 95%CI = 1.012-1.631). In the subgroup analyses according to smoking status, no significant association was detected in all

  14. The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis.

    PubMed

    Kong, Xiang-Zhen; Zhang, Zheng-Yi; Wei, Lian-Hua; Li, Rui; Yu, Jing

    2017-02-11

    BACKGROUND Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association. MATERIAL AND METHODS PubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk. RESULTS Fifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53-1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03-3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56-1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79-3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism. CONCLUSIONS In this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations.

  15. The Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism Increases Myocardial Infarction Risk: A Meta-Analysis

    PubMed Central

    Kong, Xiang-Zhen; Zhang, Zheng-Yi; Wei, Lian-Hua; Li, Rui; Yu, Jing

    2017-01-01

    Background Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association. Material/Methods PubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk. Results Fifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53–1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03–3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56–1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79–3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism. Conclusions In this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations. PMID:28188309

  16. Analysis of the Relationship between Antioxidant Enzyme Gene Polymorphisms and Their Activity in Post-Traumatic Gonarthrosis.

    PubMed

    Vnukov, V V; Panina, S B; Milyutina, N P; Krolevets, I V; Zabrodin, M A

    2016-05-01

    Analysis of polymorphisms of genes encoding antioxidant enzymes SOD1 (G7958A), SOD2 (T58C), CAT (C-262T), and GSTP1 (Ile105Val) in 93 patients with post-traumatic gonarthrosis showed that GSTP1 Ile105Val polymorphism is often associated with heterozygous mutation in catalase gene CAT C-262T. In gonarthrosis, catalase activity in peripheral blood mononuclear cells in patients with CT genotype of the C-262T locus of CAT gene more than 2-fold surpassed that in CC genotype and more than 50% surpassed the normal. Changes in the balance of activity of antioxidant enzymes can affect viability of mononuclear cells.

  17. Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis.

    PubMed

    Zhang, He; Sun, Zhao-qing; Liu, Shuang-shuang; Yang, Li-na

    2016-01-01

    The role of GRK4 and DRD1 genes in hypertension remains controversial. We performed a meta-analysis to determine whether GRK4 and DRD1 polymorphisms influence the risk of hypertension and examined the relationship between the genetic variances and the etiology of hypertension. Relevant case-control studies were retrieved by database searches and selected according to established inclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, and sensitivity analysis were performed. A total of 15 articles containing 29 studies were finally included. In the dominant model, rs4532 locus of DRD1 gene was related to hypertension with a pooled OR of 1.353 (95% CI =1.016-1.802, P=0.038). Subgroup analysis for ethnicity showed that rs1024323 locus of GRK4 gene was associated with hypertension in Caucasians (OR =1.826, 95% CI =1.215-2.745, P=0.004) but not in East Asians and Africans. Rs4532 locus was associated with hypertension in East Asians (OR =1.833, 95% CI =1.415-2.376, P,0.001) but not in Caucasians. These data provide possible references for future case-control studies in hypertension.

  18. Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis.

    PubMed

    Zhang, Jie; Xiao, Yan; Zhang, Xian-Wen; Gao, Zhi-Qing; Han, Jing-Hui

    2014-07-01

    Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR = 0.76, 95% CI: 0.43-1.34, p = 0.34; CC genotype: OR = 1.18, 95% CI: 0.63-2.22, p = 0.60). Interestingly, AA genotype was associated with the T2DN risk (OR = 0.68, 95% CI: 0.49-0.96, p = 0.03). In the sensitivity analysis according to the Hardy-Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (≥ 100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk.

  19. Analysis of XRCC2 and XRCC3 gene polymorphisms in pancreatic cancer

    PubMed Central

    TALAR-WOJNAROWSKA, RENATA; GĄSIOROWSKA, ANITA; OLAKOWSKI, MAREK; DRANKA-BOJAROWSKA, DARIA; LAMPE, PAWEŁ; SMOLARZ, BEATA; MAŁECKA-PANAS, EWA

    2016-01-01

    The double-strand break DNA repair pathway, including XRCC2 and XRCC3 genes, is implicated in maintaining genomic stability and therefore could affect the pancreatic cancer risk. The aim of the present study was to evaluate the clinical significance of the XRCC2 and XRCC3 gene polymorphisms in patients with pancreatic cancer. The present study included 203 patients: 101 with pancreatic cancer and 102 healthy controls. The Arg188His XRCC2 and the Thr241Met XRCC3 gene polymorphisms have been studied in DNA isolated from blood samples. The associations of the analysed genotypes and clinical data at diagnosis have been evaluated. The frequencies of the genotypes of the Arg188His XRCC2 and Thr241Met XRCC3 polymorphisms did not differ significantly between patients and controls. The study did not identify a correlation between the XRCC2 and XRCC3 genes polymorphisms and tumor size or localisation. Analysed polymorphisms were also not associated with the gender and age of the patient, or the presence of regional or distant metastases. In conclusion, the present study did not suggest an association between the Arg188His XRCC2 and the Thr241Met XRCC3 polymorphisms and the clinical data of patients with pancreatic cancer. PMID:26893845

  20. Analysis of XRCC2 and XRCC3 gene polymorphisms in pancreatic cancer.

    PubMed

    Talar-Wojnarowska, Renata; Gąsiorowska, Anita; Olakowski, Marek; Dranka-Bojarowska, Daria; Lampe, Paweł; Smolarz, Beata; Małecka-Panas, Ewa

    2016-02-01

    The double-strand break DNA repair pathway, including XRCC2 and XRCC3 genes, is implicated in maintaining genomic stability and therefore could affect the pancreatic cancer risk. The aim of the present study was to evaluate the clinical significance of the XRCC2 and XRCC3 gene polymorphisms in patients with pancreatic cancer. The present study included 203 patients: 101 with pancreatic cancer and 102 healthy controls. The Arg188His XRCC2 and the Thr241Met XRCC3 gene polymorphisms have been studied in DNA isolated from blood samples. The associations of the analysed genotypes and clinical data at diagnosis have been evaluated. The frequencies of the genotypes of the Arg188His XRCC2 and Thr241Met XRCC3 polymorphisms did not differ significantly between patients and controls. The study did not identify a correlation between the XRCC2 and XRCC3 genes polymorphisms and tumor size or localisation. Analysed polymorphisms were also not associated with the gender and age of the patient, or the presence of regional or distant metastases. In conclusion, the present study did not suggest an association between the Arg188His XRCC2 and the Thr241Met XRCC3 polymorphisms and the clinical data of patients with pancreatic cancer.

  1. Association between G-217A polymorphism in the AGT gene and essential hypertension: a meta-analysis.

    PubMed

    Yao, R; Du, Y Y; Zhang, Y Z; Chen, Q H; Zhao, L S; Li, L

    2015-05-25

    Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.

  2. Associations between nitric oxide synthase 3 gene polymorphisms and preeclampsia risk: a meta-analysis

    PubMed Central

    Zeng, Fangfang; Zhu, Sui; Wong, Martin Chi-Sang; Yang, Zuyao; Tang, Jinling; Li, Keshen; Su, Xuefen

    2016-01-01

    Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C, and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT + GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21–1.77, P < 0.001; I2 = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07–1.58, P = 0.034; I2 = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C, and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia. PMID:26997284

  3. A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS

    PubMed Central

    Wills, A -M.; Cronin, S; Slowik, A; Kasperaviciute, D; Van Es, M A.; Morahan, J M.; Valdmanis, P N.; Meininger, V; Melki, J; Shaw, C E.; Rouleau, G A.; Fisher, E M.C.; Shaw, P J.; Morrison, K E.; Pamphlett, R; Van den Berg, L H.; Figlewicz, D A.; Andersen, P M.; Al-Chalabi, A; Hardiman, O; Purcell, S; Landers, J E.; Brown, R H.

    2009-01-01

    Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding. Methods: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls. Results: The combined fixed effects odds ratio (OR) for rs662 (PON1 Q192R) was 1.09 (95% confidence interval [CI], 1.02–1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07–1.45, p = 0.0004); the combined OR for rs854560 (PON1 L55M) was 0.97 (95% CI, 0.86–1.10, p = 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92–1.27, p = 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97–1.16, p = 0.22). Conclusions: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS. GLOSSARY ALS = amyotrophic lateral sclerosis; CI = confidence interval; GWAS = genome-wide association studies; OR = odds ratio; SALS = sporadic ALS; SNP = single nucleotide polymorphism. PMID:19321847

  4. Association of C722T polymorphism in XRCC3 gene with larynx cancer: a meta-analysis.

    PubMed

    Li, Dong; You, Hui-Hua; Jia, Yuan-Jing; Guo, Jian-Dong; Du, Huan-Le

    2014-06-01

    Several case-control studies indicated that XRCC3 genetic polymorphism (C722T) was associated with larynx cancer. The present study aimed to further evaluate the relation between the XRCC3 gene C722T polymorphism and larynx cancer. We selected five case-control studies related to XRCC3 gene C722T polymorphism and larynx cancer by searching PubMed, EMBase, Chinese CNKI, and Wanfang database. RevMan 5.0 software was used to perform the analysis. We directly utilized Q test and I (2) test to test the heterogeneity between each study. We utilized the fixed effects model to merge the odds ratio (OR) and 95 % confidence interval. There were 1,507 larynx cancer patients and 3,623 cancer-free control subjects included in the present study. By meta-analysis, we did not find any association of XRCC3 gene C722T polymorphism with larynx cancer [OR=1.54, 95 % CI (0.77-3.08); P=0.22]. The present study indicated that XRCC3 gene C722T polymorphism was not associated with larynx cancer.

  5. Discs Large Homolog 5 (DLG5) Gene Polymorphism and Crohn's Disease: A Meta-Analysis of the Published Studies.

    PubMed

    Shafieyoun, Arezoo; Moraveji, Sharareh; Bashashati, Mohammad; Rezaei, Nima

    2016-05-01

    The real pathophysiology of Crohn's disease is unknown. The higher prevalence of Crohn's disease in Caucasian and Jewish ethnicities, as well as its familial aggregation and higher concordance among monozygotic twins, suggest some roles for genes in its development, clinical progression, and outcome. Recent original studies have indicated DLG5113G/A gene polymorphism as a risk factor for Crohn's disease. Meanwhile, the results of these studies are not consistent. We performed the current meta-analysis to understand whether there is any association between DLG5 gene polymorphism and the risk of Crohn's disease. PubMed was searched to find the case-control studies on DLG5 gene polymorphisms and Crohn's disease. This search compiled 65 articles and based on our criteria. 11 articles were included in this meta-analysis. The association between the DLG5 113G/A polymorphism and the risk of disease was assessed using odds ratio (OR) and 95% confidence interval (95% CI). Heterogeneity was evaluated based on I2 values.  Random and fixed-effect models were used when I2>50% and I2≤50%, respectively. Eleven studies with a total of 4648 cases and 5677 controls were pooled. Based on our meta-analysis, DLG5113G/A gene polymorphism both at genotypic and allelic levels were not associated with the risk of Crohn's disease. Pooled data indicated no significant association between DLG5113G/A gene polymorphism and the development of Crohn's disease. In order to achieve a superior conclusion, multicenter studies on larger number of patients are recommended.

  6. Impact of single nucleotide polymorphisms in HBB gene causing haemoglobinopathies: in silico analysis.

    PubMed

    George Priya Doss, C; Rao, Sethumadhavan

    2009-04-01

    Single nucleotide polymorphisms (SNPs) are being intensively studied to understand the biological basis of complex traits and diseases. Deleterious mutations of the human beta-globin gene (HBB) are responsible for beta-thalassaemia and other haemoglobinopathies, which are the most common genetic diseases of blood. Single amino acid substitutions in the globin chain are the commonest forms of haemoglobinopathy. Although many haemoglobinopathies present similar structural abnormal points, their functions sometimes are different. Here, using computational methods, we analysed the genetic variations that can alter the expression and function of the HBB gene. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 210 (90%) non-synonymous (ns)SNPs were found to be deleterious. The structure-based approach PolyPhen server suggested that 134 (57%) nsSNPS may disrupt protein function and structure. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutation that occurred in the native protein coded by the HBB gene in HbC, HbD, HbE and HbS. The amino acid residues in the native and mutant modelled protein were further analysed for solvent accessibility, and secondary structure to check the stability of the proteins. The functional analysis presented here may be a good model for further research.

  7. GENETIC ANALYSIS OF THE IL8 GENE POLYMORPHISM (rs4073) IN GENERALIZED AGGRESSIVE PERIODONTITIS

    PubMed Central

    Andia, Denise Carleto; Letra, Ariadne; Casarin, Renato Corrêa Viana; Casati, Marcio Zaffalon; Line, Sergio Roberto Peres; de Souza, Ana Paula

    2012-01-01

    Objectives Interleukin (IL)-8 is an important chemokine for regulation of the inflammatory response. A single nucleotide polymorphism (SNP) reference sequence (rs) 4073 in the IL8 gene has been shown to regulate IL-8 levels after stimulation with lipopolysaccharide. This study investigates the transmission pattern of the IL8 rs4073 risk allele A and its association with susceptibility to Aggressive Periodontitis (AgP) in families and in a case-control cohort of unrelated individuals from a Brazilian population. Design Genotyping was performed by standard polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) in 13 nuclear families and 184 unrelated subjects. Statistical analysis was performed using the transmission disequilibrium test (TDT) for the family dataset and chi-square test and multivariate logistic regression modeling for the case-control dataset. Results TDT analyses did not detect evidence of over transmission of IL8 rs4073 alleles in affected and unaffected family members (allele T: 52%; allele A: 48%; p = 0.2252). How expected, analyses of cases and unrelated controls showed a significant and inverse association of age with AgP; however, a lack of association between genotypes, ethnic groups and generalized AgP was observed. Conclusions The SNP (rs4073) was not associated with AgP in unrelated individuals and there is no evidence of over transmission of the alleles in families with AgP, from Brazilian individuals. PMID:22727395

  8. Genetic analysis of the IL8 gene polymorphism (rs4073) in generalized aggressive periodontitis.

    PubMed

    Andia, Denise Carleto; Letra, Ariadne; Casarin, Renato Corrêa Viana; Casati, Marcio Zaffalon; Line, Sergio Roberto Peres; de Souza, Ana Paula

    2013-02-01

    Interleukin (IL)-8 is an important chemokine for regulation of the inflammatory response. A single nucleotide polymorphism (SNP) reference sequence (rs) 4073 in the IL8 gene has been shown to regulate IL-8 levels after stimulation with lipopolysaccharide. This study investigates the transmission pattern of the IL8 rs4073 risk allele A and its association with susceptibility to aggressive periodontitis (AgP) in families and in a case-control cohort of unrelated individuals from a Brazilian population. Genotyping was performed by standard polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) in 13 nuclear families and 184 unrelated subjects. Statistical analysis was performed using the transmission disequilibrium test (TDT) for the family dataset and Chi-square test and multivariate logistic regression modelling for the case-control dataset. TDT analyses did not detect evidence of over transmission of IL8 rs4073 alleles in affected and unaffected family members (allele T: 52%; allele A: 48%; p=0.2252). How expected, analyses of cases and unrelated controls showed a significant and inverse association of age with AgP; however, a lack of association between genotypes, ethnic groups and generalized AgP was observed. The SNP (rs4073) was not associated with AgP in unrelated individuals and there is no evidence of over transmission of the alleles in families with AgP, from Brazilian individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Association between the FCGR2A gene H131R polymorphism and risk of Kawasaki disease: a meta-analysis.

    PubMed

    Lin, L; Wang, S Y; Yang, S B; Xiao, F C

    2015-06-11

    Several previous studies have investigated whether the FCGR2A gene H131R polymorphism confers an increased risk of Kawasaki disease (KD), but conflicting results have been reported. To further explore the association of this polymorphism with KD susceptibility, we performed an extensive search of relevant studies and conducted a meta-analysis to obtain a more precise estimate of risk. Systematic searches of the electronic databases Embase, PubMed, and Google Scholar were performed to identify relevant studies. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used for statistical analysis. Six studies were included in the meta-analysis, involving 1709 patients with KD and 3207 controls. Significant association was found between the FCGR2A gene H131R polymorphism and KD risk in analysis of the total population (HH vs RR: OR = 1.97, 95%CI = 1.55-2.50; HH vs HR: OR = 1.38, 95%CI = 1.21-1.57; the dominant model: OR = 0.69, 95%CI = 0.60-0.78; and the recessive model: OR = 1.65, 95%CI = 1.32-2.07). In subgroup analysis by ethnicity, significant association was found between the H131R polymorphism and KD risk in Asians, but not in Caucasians. In addition, we found no significant association between the FCGR2A gene H131R polymorphism and risk of KD-associated coronary artery lesions. In conclusion, this meta-analysis suggested that the H131R polymorphism in the FCGR2A gene might be associated with susceptibility to KD in Asians.

  10. Association of CYP1B1 gene polymorphisms with susceptibility to endometrial cancer: a meta-analysis.

    PubMed

    Wang, Fang; Zou, Yan-Feng; Sun, Guo-Ping; Su, Hong; Huang, Fen

    2011-03-01

    The objective of this meta-analysis was to quantitatively summarize the association of CYP1B1 gene polymorphisms and endometrial cancer risk. Data were collected from the following electronic databases: PubMed,Elsevier Science Direct, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure and Wanfang, with the last report up to June 2010. Meta-analysis was conducted in a fixed/random effect model. Out of the 715 papers retrieved 12 studies (3605 cases and 5692 controls) on the association of CYP1B1 gene polymorphisms with endometrial cancer risk in different ethnic groups were identified. Meta-analysis was performed for CYP1B1 gene polymorphisms: R48G (C/G, five studies), L432V (C/G, 12 studies), N453S (A/G, four studies), and A119S (G/T, five studies). We did not detect any association of CYP1B1 gene A119S polymorphism with endometrial cancer. An association of CYP1B1 gene R48G polymorphism with endometrial cancer was found [GG vs. GC+CC: odds ratio (OR)=0.55, 95% confidence interval (CI): 0.42-0.73, P<0.0001; GG vs. CC: OR=0.46, 95% CI: 0.23-0.91, P=0.03]. We found that CYP1B1 gene L432V polymorphism was associated with a significantly increased risk of endometrial cancer (G vs. C: OR=1.23, 95% CI: 1.06-1.43, P=0.007; GC+GG vs. CC:OR=1.24, 95% CI: 1.08-1.43, P=0.003; GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). Moreover, we detected the association of CYP1B1 gene N453S polymorphism with endometrial cancer (G vs. A: OR=0.82,95% CI: 0.72-0.94, P=0.005; GA vs. AA: OR=0.81, 95% CI: 0.69-0.95, P=0.01). In conclusion, this meta-analysis provides strong evidence that CYP1B1 gene R48G, L432V, and N453S polymorphisms are associated with endometrial cancer risk, but not A119S.

  11. Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

    PubMed Central

    Yadav, Sunaina; Hasan, Nazeeha; Marjot, Thomas; Khan, Muhammad S.; Prasad, Kameshwar; Bentley, Paul; Sharma, Pankaj

    2013-01-01

    The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling. PMID:23505425

  12. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects

    PubMed Central

    Pishva, Seyyed Reza; Vasudevan, Ramachandran; Etemad, Ali; Heidari, Farzad; Komara, Makanko; Ismail, Patimah; Othman, Fauziah; Karimi, Abdollah; Sabri, Mohammad Reza

    2013-01-01

    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects. PMID:23358257

  13. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects.

    PubMed

    Pishva, Seyyed Reza; Vasudevan, Ramachandran; Etemad, Ali; Heidari, Farzad; Komara, Makanko; Ismail, Patimah; Othman, Fauziah; Karimi, Abdollah; Sabri, Mohammad Reza

    2013-01-28

    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects.

  14. Role of Interleukin-10 (-1082A/G) gene polymorphism with the risk of ischemic stroke: a meta-analysis.

    PubMed

    Kumar, Pradeep; Yadav, Arun Kumar; Misra, Shubham; Kumar, Amit; Chakravarty, Kamalesh; Prasad, Kameshwar

    2016-09-01

    The role of anti-inflammatory Interleukin-10 (IL-10) cytokine gene polymorphism with the risk of ischemic stroke (IS) remains controversial. The aim of present meta-analysis was to investigate the association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS. A literature search for candidate gene association studies published before 29 February 2016 was conducted in the PubMed, EMBASE, Google Scholar, and TRIP database. The following search terms were used: 'Interleukin-10' or 'IL-10' and 'Ischemic stroke' or 'IS' and 'Cerebral Infarction' or 'CI' and 'genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'. Fixed or random effects models were used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias. In our meta-analysis, five case-control studies involving 1209 IS cases and 1139 controls were included. Overall, there was no significant association between IL-10 (-1082 A/G) [rs1800896] and risk of IS under dominant [AA + AG vs. GG], recessive [AA vs. AG + GG], and allelic [G vs.A] models. However, based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, we observed significant association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS for Large Vessel Disease (LVD), Small Vessel Disease (SVD), and other (others due to determined and undetermined etiology) subtypes of IS. This is the first meta-analysis to conclude that IL-10-1082A/G gene polymorphism is associated with the risk of LVD, SVD, and other subtypes of IS. Further well-designed large sample size studies based on TOAST classification are needed to validate these findings.

  15. Association analysis of the functional MAOA gene promoter and MAOB gene intron 13 polymorphisms in tension type headache patients.

    PubMed

    Edgnülü, Tuba G; Özge, Aynur; Erdal, Nurten; Kuru, Oktay; Erdal, Mehmet E

    2014-01-01

    Monoamine oxidase (MAO) enzymes play an important role in the etiology of many neurological diseases. Tension type headache (TTH) treatments contain inhibitors for selective re-uptake of serotonin and monoamine oxidase inhibitors. MAO (EC 1.4.3.4) has two isoenzymes known as MAOA and MAOB. A promoter polymorphism of a variable number of tandem repeats (VNTR) in the MAOA gene seems to affect MAOA transcriptional activity in vitro. Also, G/A polymorphism in intron 13 (rs1799836) of the MAOB gene have been previously found to be associated with the variability of MAOB enzyme activity. The aim of our study was to investigate a possible association of monoamine oxidase (MAOA and MAOB) gene polymorphisms in tension type headache. MAO gene polymorphisms were examined in a group of 120 TTH patients and in another 168 unrelated healthy volunteers (control group). MAOA promoter and MAOB intron 13 polymorphisms were genotyped using PCR-based methods. An overall comparison between the genotype of MAOA and MAOB genes and allele frequencies of the patients and the control group did not reveal any statistically significant difference between the patients and the control group (p=0.162). Factors like estrogen dosage, the limited number of male patients and other genes' neurotransmitters involved in the etiology of TTH could be responsible for our non-significant results.

  16. A meta-analysis of xeroderma pigmentosum gene D Ls751Gln polymorphism and susceptibility to hepatocellular carcinoma.

    PubMed

    Wang, Yu; Zhao, Yingren; Zhang, Aiyun; Ma, Juan; Wang, Zhenzhen; Zhang, Xu

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of most common malignant tumors worldwide, but with unclear mechanisms. Xeroderma pigmentosum gene D (XPD) is one important DNA damage repair gene and can be involved in protein mutation. Currently little has been known about XPD polymorphism and HCC susceptibility in Chinese people. This study used a meta-analysis approach to comprehensively investigate the correlation between XPD polymorphism and HCC susceptibility in Chinese population, based on previously published literatures. A computer retrieval system was used to collect all case-control studies about XPD Lys751Gln polymorphism and HCC susceptibility. Data in literatures were extracted for meta-analysis. After the primary screening, four independent studies, which were published in 3 English articles and one Chinese article, were recruited in this study. There were 1,717 samples included in all studies. Using Gln/Gln + Lys/Gln, Lys/Lys + Lys/Gln and Lys allels as the reference, HCC disease alleles including Lys/Lys, Gln/Gln and Gln had OR values (95% CI, I(2)) of 1.007 (0.657~4.672, 91%), 3.516 (0.220~20.661, 48%) and 3.225 (0.278~12.326, 84%), respectively. The polymorphism of XPD751 loci is closely correlated with primary HCC. Lys751Gln polymorphism of XPD gene can be used as one susceptibility factor for HCC.

  17. [Correlation analysis of G870A CCND1 gene polymorphism with digestive system tumors].

    PubMed

    Yang, Shu-Min; Shi, Ya-Lin

    2016-11-20

    To study the correlation of G870A CCND1 gene polymorphism and digestive system tumors. From August 2010 to August 2014, 164 digestive system cancer patients (including 82 patients with gastric cancer and 82 with colorectal cancer) and 82 healthy subjects (control group) were examined with PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1 gene G870A frequency in the 3 groups and its association with tumor staging and grading were analyzed. The frequencies of the GG, GA and AA genotypes in G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer differed significantly from those in the control group (P<0.05). G870A CCND1 gene polymorphism was closely associated with an increased risk of digestive system tumors (P<0.05). The GA and AA genotypes were associated with a significantly higher risk of digestive system cancer risk than the GG genotype (P<0.05), and their frequencies were significantly higher in patients with tumors of higher pathological grade and in those in advanced tumor stages (P<0.05). G870A CCND1 gene polymorphism is associated with the risk of digestive system tumors. The allele A is associated with an increased risk of digestive system tumors and correlated with the tumor differentiation and staging of the tumor.

  18. Association between the -607 C > A polymorphism in interleukin-18 gene promoter with gastrointestinal cancer risk: a meta-analysis.

    PubMed

    Yao, J; Li, Z H; Li, Y X; Zhang, R; Zhang, D G; Xu, Z L; Wang, L S; Wang, J Y

    2015-12-14

    The interleukin-18 (IL-18) gene -607 C/A polymorphism has been reported to be associated with gastrointestinal cancer, but there are conflicting results from previous studies on said topic. Therefore, the aim of this meta-analysis is to derive a more precise estimation of the association between the -607 C/A polymorphism in the IL-18 gene and gastrointestinal cancer risk. Literature searches of PubMed, Google Scholar, and Web of Science databases were carried out in 2015. Five studies were assessed with a total of 1618 cases and 1155 healthy controls. When results from all eligible studies were pooled into the meta-analysis, we found significant association between the IL-18 gene -607 C/A polymorphism and gastrointestinal cancer risk (CC vs AA: OR = 0.93, 95%CI = 0.72- 1.20; CC vs CA: OR = 0.76, 95%CI = 0.62-0.92; dominant model: OR = 1.25, 95%CI = 1.03-1.50; recessive model: OR = 1.09, 95%CI = 0.87-1.37). In the subgroup analysis, significant associations between the -607 C/A polymorphism and gastrointestinal cancer risk were found in esophageal cancer. However, this polymorphism did not appear to have any influence on gastric cancer and colorectal cancer susceptibility. In conclusion, this meta-analysis suggests that the -607 C/A polymorphism in the IL-18 gene may be associated with susceptibility to esophageal cancer. Further studies with large sample sizes are needed to confirm these conclusions.

  19. The Association between ANXA11 Gene Polymorphisms and Sarcoidosis: a Meta-Analysis and systematic review.

    PubMed

    Zhou, Hongfei; Diao, Mengyuan; Zhang, Mingyue

    2016-08-01

    The associations of ANXA11 gene polymorphisms and susceptibility to sarcoidosis have been evaluated in recent years. However, the results remain controversial, especially in different ethnicity. To assess the associations between ANXA11 and sarcoidosis, we conducted this meta-analysis. Articles were searched in MEDLINE, EMBASE and PubMed from their establishment date to August of 2014, and 4,567 sarcoidosis patients and 4,278 controls from 6 studies were included. The strength of associations was determined by ORs with 95% CIs. The associations between ANXA11 SNP rs1049550, rs2573346, rs2789679 polymorphisms and sarcoidosis risk were assessed using additive, recessive and dominant models. ANXA11 SNP rs2573346 and rs2789679 T allele conferred protection against sarcoidosis (OR: 0.664, 95% CI: 0.607-0.726 for rs2573346, and OR: 0.698, 95% CI: 0.640-0.762 for rs2789679). For SNP rs1049550, individuals carrying the ''T'' allele (TT+CT) had a nearly 46% increased risk for the development of sarcoidosis, when compared with CC homozygotes (OR: 1.461, 95% CI: 1.183-1.803) in overall population. A significant association was also found in additive model (OR: 1.477, 95% CI: 1.328-1.642 for CC vs. CT; OR: 0.610, 95% CI: 0.412-0.905 for TT vs. CC). In addition, ethnicity factors may contribute to the disease risk. The meta-analysis revealed that ''T'' allele of ANXA11 SNP rs2573346 and rs2789679 conferred protection against sarcoidosis. ''C'' allele of SNP rs1049550 may be a risk factor for sarcoidosis in overall population. Our study shows that ANXA11 closely associated with the development of sarcoidosis but further studies in different ethnicity were needed.

  20. Analysis of the association between lactotransferrin (LTF) gene polymorphism and dental caries.

    PubMed

    Azevedo, Luiza Foltran; Pecharki, Giovana Daniela; Brancher, João Armando; Cordeiro, Carlos Alberto; Medeiros, Kamilla Gabriella dos Santos; Antunes, Alessandra Armstrong; Arruda, Eduardo Silva; Werneck, Renata Iani; de Azevedo, Luciana Reis; Mazur, Rui Fernando; Moysés, Samuel Jorge; Moysés, Simone Tetü; Faucz, Fábio Rueda; Trevilatto, Paula Cristina

    2010-01-01

    The present study evaluated the association between lactotransferrin (LTF) gene polymorphism (exon 2, A/G, Lys/Arg) and dental caries. A convenience sample of 110 individuals, 12 years old, was divided into: group 1, 48 individuals without caries experience (DMFT=0), and group 2, 62 subjects with caries experience (DMFT>or=1). DNA was obtained from a mouthwash with 3% glucose solution, followed by a scrapping of the oral mucosa. After DNA purification, polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) was performed to access the study polymorphism. The LTF A/G (Lys/Arg) polymorphism had been previously reported as located in exon 1. Allele 1 of the study polymorphism was associated with low DMFT index and showed a protective effect against caries experience (OR=0.16, IC=0.03-0.76, p=0.01). Lactotransferrin A/G (exon 2, Lys/Arg) polymorphism was associated with susceptibility to dental caries in 12-year-old students.

  1. Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of pulmonary tuberculosis: meta-analysis.

    PubMed

    Chen, Zhi; Wang, Wei; Liang, Jianqin; Wang, Jinhe; Feng, Shisheng; Zhang, Guangyu

    2015-05-08

    Previous studies indicated that the single nucleotide polymorphisms (SNPs) in TLR9 gene might be associated with Tuberculosis (TB) risk. However, the results are inconsistent and inconclusive. 1745 articles from four databases were involved in our study. A meta-analysis on the associations between the seven polymorphisms and TB risk was carried out by comparison using different genetic models. In this systematic review 8 studies from seven English articles were analyzed. Our results showed that rs352139 is significantly associated with TB risk (AA vs. AG, OR 0.77, 95% CI 0.65-0.92, P = 0.004). In the ethnic subgroup analysis, Indonesians with AA genotype had a decreased susceptibility while Mexicans with GG allele had an increased risk. The meta-analysis indicated that rs352139 polymorphism might be associated with decreased TB risk in Indonesians whereas increased risk in Mexicans. Whether the observed association was due to causal effect needs to be further studied.

  2. Ewing's sarcoma: analysis of single nucleotide polymorphism in the EWS gene.

    PubMed

    Silva, Deborah S B S; Sawitzki, Fernanda R; De Toni, Elisa C; Graebin, Pietra; Picanco, Juliane B; Abujamra, Ana Lucia; de Farias, Caroline B; Roesler, Rafael; Brunetto, Algemir L; Alho, Clarice S

    2012-11-10

    We aimed to investigate single nucleotide polymorphisms (SNPs) in the EWS gene breaking region in order to analyze Ewing's sarcoma susceptibility. The SNPs were investigated in a healthy subject population and in Ewing's sarcoma patients from Southern Brazil. Genotyping was performed by TaqMan® assay for allelic discrimination using Real-Time PCR. The analysis of incidence of SNPs or different SNP-arrangements revealed a higher presence of homozygote TT-rs4820804 in Ewing's sarcoma patients (p=0.02; Chi Square Test). About 300 bp from the rs4820804 SNP lies a palindromic hexamer (5'-GCTAGC-3') and three nucleotides (GTC), which were previously identified to be in close vicinity of the breakpoint junction in both EWS and FLI1 genes. This DNA segment surrounding the rs4820804 SNP is likely to indicate a breakpoint region. If the T-rs4820804 allele predisposes a DNA fragment to breakage, homozygotes (TT-rs4820804) would have double the chance of having a chromosome break, increasing the chances for a translocation to occur. In conclusion, the TT-rs4820804 EWS genotype can be associated with Ewing's sarcoma and the SNP rs4820804 can be a candidate marker to understand Ewing's sarcoma susceptibility.

  3. The Association between VDR Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Wei; Lu, Ping

    2016-01-01

    Aims. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms with diabetic retinopathy (DR) susceptibility reported conflicting results. A systematic meta-analysis was undertaken to clarify this topic. Methods. A systematic search of electronic databases (PubMed, EMBASE, and CNKI) was carried out until March 31, 2016. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. Results. A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (649 cases and 707 controls). Pooled ORs showed a significant association between FokI polymorphism and DR risk in all the four genetic models (OR = 1.612 (1.354~1.921), 1.988 (1.481~2.668), 1.889 (1.424~2.505), and 2.674 (1.493~4.790) in allelic, dominant, recessive, and additive models, resp., PZ < 0.01), but not for TaqI or BsmI polymorphism (PZ > 0.05). Similar results were found in the subgroup analysis. Sensitivity analysis indicated that the results were relatively stable and reliable. Results of Begg's and Egger's tests suggested a lack of publication bias. Conclusions. Our meta-analysis demonstrated that DR was significantly associated with VDR gene FokI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be done to confirm the findings. PMID:27891515

  4. Polymorphism Analysis of VSX1 and SOD1 Genes in Greek Patients with Keratoconus.

    PubMed

    Moschos, Marilita M; Kokolakis, Nikolaos; Gazouli, Maria; Chatziralli, Irini P; Droutsas, Dimitrios; Anagnou, Nicholas P; Ladas, Ioannis D

    2015-01-01

    A number of mutations in the VSX1 and SOD1 genes have been reported to be associated with keratoconus (KC), however the results from different studies are controversial. In this study, we conducted the genotyping of common polymorphisms [VSX1: D144E, H244R, R166W, G160D; SOD1: intronic 7-base deletion (c.169 + 50 delTAAACAG)], in a case-control sample panel of the Greek population. A case-control panel, with 33 KC patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the VSX1: D144E, H244R, R166W, G160D and SOD1: intronic 7-base deletion (c.169 + 50 delTAAACAG) polymorphisms by direct sequencing. We observed no polymorphisms of the VSX1 gene in the case-control panel. Concerning the SOD1 intronic 7-base deletion (c.169 + 50 delTAAACAG), our findings suggest that heterozygous carriers are over-represented among KC cases compared to healthy controls (p = 0.002). We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the pathogenesis of KC. Further studies are required to identify other important genetic factors involved in the pathogenesis and progression of KC.

  5. Association of tumor necrosis factor-α gene G-308A polymorphism with dilated cardiomyopathy: a meta-analysis.

    PubMed

    Luo, Rong; Li, Xiaoping; Fan, Xiongwei; Yuan, Wuzhou; Wu, Xiushan

    2013-03-01

    Published data on the association between tumor necrosis factor-α (TNF-α) G-308A gene polymorphism and dilated cardiomyopathy (DCM) risk are inconclusive. To clarify the association of TNF-α G-308A gene polymorphism and DCM, a meta-analysis of case-control studies was performed. Some databases, such as PubMed and Embase, were searched to indentify related studies. Search terms included dilated cardiomyopathy, tumor necrosis factor-alpha or TNF-α or TNF alpha or tumor necrosis factor alpha, and polymorphism or mutation. Eight case-control studies involving 1487 DCM cases and 1734 normal controls were included in the meta-analysis to assess the purported association between the TNF-α G-308A gene polymorphism and the risk of DCM. A dominant genetic model was used and the comparison of GA/AA genotype versus GG genotype was performed in the present meta-analysis. The odds ratio was 1.42 (95% confidence interval: 1.05, 1.93, P=0.02), manifesting frequency of the TNF-α-308 GA/AA genotype was higher in DCM patients than the control group. TNF-α G-308A nucleotide transition might be associated with the risk of DCM.

  6. Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis.

    PubMed

    Liu, Chibo; Liu, Liu

    2011-12-01

    Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and paraoxonase 1 (PON1) genes have been considered to be implicated in the development of breast cancer. However, the results were inconsistent. In this study, a meta-analysis was performed to assess the associations of five polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and PON1 Q192R polymorphisms, with breast cancer risk. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Three studies (2,003 cases and 1,967 controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476 controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573 controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379 controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283 controls) for PON1 Q192R polymorphism were included in the meta-analysis. Overall, the results showed null significant association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk; however, PON1 L55M was significantly associated with breast cancer risk overall (MM vs. LL: OR = 2.16; 95% CI, 1.76-2.66). For LEPR Q223R polymorphism, further subgroup analysis suggested that the association was only statistically significant in East Asians (OR = 0.50; 95% CI, 0.36-0.70) but not in Caucasians (OR = 1.06; 95% CI, 0.77-1.45) or Africans (OR = 1.30; 95% CI, 0.83-2.03). The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1 L55M might increase breast cancer risk. However, given the limited

  7. Lack of association of P2RX7 gene rs2230912 polymorphism with mood disorders: a meta-analysis.

    PubMed

    Feng, Wen-Ping; Zhang, Bo; Li, Wen; Liu, Juan

    2014-01-01

    To assess the association of P2RX7 gene rs2230912 polymorphism with mood disorders using a meta-analysis. Data were collected from the following electronic databases: PubMed, Excerpta Medica Database, Elsevier Science Direct, Cochrane Library, and Chinese Biomedical Literature Database, with the last report up to April 1, 2013. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Dependent on the results of heterogeneity test among individual studies, the fixed effect model (Mantel-Haenszel) or random effect model (DerSimonian-Laird) was selected to summarize the pooled OR. We identified 13 separate studies using search (6,962 cases and 9,262 controls). We detected significant between-study heterogeneity. No significant association of this polymorphism with mood disorders was found (P>0.05). We also performed disease-specific meta-analysis in unipolar depression and bipolar disorder. No significant association of this polymorphism with unipolar depression or bipolar disorder was found (P>0.05). Additionally, we performed subgroup analysis by different types of cases. No significant association of this polymorphism with mood disorders in clinical cohorts or population-based cohorts (P>0.05). A significant association of this polymorphism with mood disorders was found for the allele contrast in family-based cohorts (OR = 1.26, 95%CI = 1.05-1.50, P = 0.01). Overall, our meta-analysis suggests that P2RX7 gene rs2230912 polymorphism may not contribute to the risk of developing mood disorders using a case-control design. Given the discordance in the subgroup analysis by different types of cases, further studies based on larger sample size are still needed.

  8. Analysis of IL-33 gene polymorphism (rs11792633 C/T) and risk of schizophrenia

    PubMed Central

    Kordi-Tamandani, Dor Mohammad; Bahrami, Ahmad Reza; Sabbaghi-Ghale-no, Raziye; Soleimani, Hanieh; Baranzehi, Tayebe

    2016-01-01

    Recently, inflammation has been found to be a significant factor in the development of Schizophrenia (SCZ). The aim of the present research was to investigate whether interleukin-33 (IL-33, OMIM: 608678) gene polymorphism (rs11792633, C/T) is associated with the development of SCZ or not. DNA was isolated from the serum of 70 patients with SCZ and 70 healthy controls. The PCR based method was used for detection of the IL-33 polymorphism. The CT (OR=0.05, 95% CI: 0.003-0.057, P<0.001) and TT (OR=0.12, 95% CI: 0.028-0.46, P<0.001) genotypes significantly decreased the risk of SCZ. Our present findings indicate that the IL-33 polymorphism associated with the risk of SCZ. PMID:27844019

  9. Polymorphisms in the intercellular adhesion molecule 1 gene and cancer risk: a meta-analysis

    PubMed Central

    Tang, Weifeng; Wang, Yafeng; Chen, Yuanmei; Gu, Haiyong; Chen, Shuchen; Kang, Mingqiang

    2015-01-01

    Objectives: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis. Design and methods: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate. Results: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility. Conclusions: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians. PMID:26550112

  10. Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a meta-analysis.

    PubMed

    Li, Su-Xia; Dai, Qiang-Sheng; Chen, Su-Xiu; Zhang, Shao-Dan; Liao, Xiao-Yu; Deng, Xia; Chi, Hong-Bo; Li, Feng-Jie; Zhu, Jin-Hong; Jiang, Yi-Yan

    2014-04-01

    Numerous epidemiological studies have been conducted to investigate the association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn (rs1799793 G > A) and Lys751Gln (rs13181 A > C) polymorphisms and bladder cancer risk; however, the conclusions remain controversial. With this in mind, we performed this meta-analysis with 11 studies including 3,797 cases and 5,094 controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls for Lys751Gln polymorphism. We searched available literatures from PubMed, Embase, and CBM databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Moreover, to validate biological plausibility of our findings, the effects of these two polymorphisms on XPD gene expression within three ethnicities was determine by gene expression analysis based on imputed genotypes from HapMap. Overall, the variant allele of Asp312Asn polymorphism was associated with an increased risk of bladder cancer (Asn/Asn vs. Asp/Asp: OR = 1.51, 95% CI = 1.19-1.91; Asp/Asn vs. Asp/Asp: OR = 1.23, 95% CI = 1.12-1.35; recessive model: OR = 1.33, 95% CI = 1.10-1.61; dominant model: OR = 1.32, 95% CI = 1.14-1.52; and allele comparing: OR = 1.26, 95% CI = 1.11-1.42). We found the Lys751Gln was associated with increased bladder cancer risk only under the recessive model (OR = 1.14, 95% CI = 1.01-1.29). Stratification analyses demonstrated an increased risk for Asians and hospital-based studies under all genetic models while only under the dominant model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn polymorphism can significantly influence mRNA expression levels among Asians and Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians. Despite some limitations, this meta-analysis suggests that polymorphisms in XPD gene may contribute to

  11. Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

    PubMed

    He, Mei; Yan, Hong; Duan, Zhao-Xia; Qu, Wei; Gong, Hai-Yan; Fan, Zheng-Li; Kang, Jian-Yi; Li, Bing-Cang; Wang, Jian-Min

    2013-01-01

    Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test.

  12. Association Analysis of MET Gene Polymorphism with Papillary Thyroid Carcinoma in a Chinese Population

    PubMed Central

    Ning, Lifeng; Yu, Yaqin; Liu, Xiaoli; Ai, Lizhe; Zhang, Xin; Rao, Wenwang; Shi, Jieping; Sun, Hui; Yu, Qiong

    2015-01-01

    To investigate the association of MET SNPs with gender disparity in thyroid tumors, as well as the metastasis and prognosis of patients, 858 patients with papillary thyroid carcinoma (PTC), 556 patients with nodular goiter, and 896 population-based normal controls were recruited. The genotyping of MET SNPs was carried out using the Sequenom MassARRAY system. The distribution of MET SNPs (rs1621 and rs6566) was different among groups. Gender stratification analysis revealed a significant association between the rs1621 genotype and PTC in female patients (P = 0.037), but not in male patients (P > 0.05). For female patients, the rs1621 AG genotype was significantly higher in patients with PTC than in normal controls (P = 0.01) and revealed an increasing risk of PTC (OR: 1.465, 95% CI: 1.118–1.92). However, association analysis of the rs1621 genotype with metastasis and prognosis revealed no significant correlation in both male and female patients. The findings of our study showed that polymorphism of SNP locus rs1621 in MET gene may be associated with gender disparity in PTC. Higher AG genotypes in rs1621 were correlated with PTC in female patients, but not in male patients. PMID:26649038

  13. Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

    PubMed

    Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong

    2012-02-01

    Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.

  14. Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

    PubMed

    Beltrán-Valero de Bernabé, D; Granadino, B; Chiarelli, I; Porfirio, B; Mayatepek, E; Aquaron, R; Moore, M M; Festen, J J; Sanmartí, R; Peñalva, M A; de Córdoba, S R

    1998-04-01

    Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles.

  15. Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

    PubMed Central

    Beltrán-Valero de Bernabé, D; Granadino, B; Chiarelli, I; Porfirio, B; Mayatepek, E; Aquaron, R; Moore, M M; Festen, J J; Sanmartí, R; Peñalva, M A; de Córdoba, S R

    1998-01-01

    Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles. PMID:9529363

  16. Analysis of methionine synthase (rs1805087) gene polymorphism in autism patients in Northern Iran.

    PubMed

    Haghiri, Rosa; Mashayekhi, Farhad; Bidabadi, Elham; Salehi, Zivar

    2016-01-01

    Autism is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social communication. The genetic and environmental factors play roles in the pathogenesis of autism. It was recently shown that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. One of the genes that may be the risk factor for autism is Methionine synthase (MTR). MTR is responsible for the regeneration of methionine from homocysteine. The aim of this study was to analyze the association of MTR A2756G gene polymorphism (rs1805087) and the risk of autism in a population in northern Iran. The prevalence of MTR A2756G polymorphism was determined in 108 children with autism and 130 controls in northern Iran. Genotypes and allele frequencies were determined in patients and controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The prevalence of genotype frequencies of AA, AG and GG in autistic children were 57.41%, 22.22% and 20.37%, respectively, while in controls were 61.54%, 32.31% and 6.15%, respectively. There was significant difference between the MTR polymorphism distribution in control and patient groups. The prevalence of allele frequencies of A and G in autistic children were 0.69 and 0.31, respectively and in controls were 0.78 and 0.22, respectively (P=0.03). The MTR G allele conferred a 1.6-fold increased risk to autism relative to the A allele (95% CI=1.06-2.41, P=0.02). The present study suggests that the G allele of MTR A2756G polymorphism is associated with an increased risk of autism.

  17. Functional analysis of polymorphisms in the promoter regions of genes on 22q11.

    PubMed

    Hoogendoorn, Bastiaan; Coleman, Sharon L; Guy, Carol A; Smith, S Kaye; O'Donovan, Michael C; Buckland, Paul R

    2004-07-01

    Segmental aneusomy, which includes chromosome 22 deletion syndrome (del(22)(q11.2q11.2)), has been associated with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face (CAF) syndrome, cat-eye syndrome (CES), der(22) syndrome, and duplication of the del(22)(q11.2q11.2) syndrome's typically deleted region. Adults with del(22)(q11.2q11.2) may develop psychiatric illnesses, including schizophrenia, schizoaffective disorder, and bipolar disorder, suggesting that lower gene dosage leads to a predisposition to these illnesses. In a bid to identify important regulatory polymorphisms (SNPs) that may emulate changes in gene dosage of the genes within the common deletion, we have analyzed the promoter region of 47 genes (44 of which encode a protein with known function) encoding proteins in and around 22q11 for sequence variants. A total of 33 of the promoters contained polymorphisms. Of those, 25 were cloned into a reporter gene vector, pGL3. The relative ability of each promoter haplotype to promote transcription of the luciferase gene was tested in each of two human cell lines (HEK293t and TE671), using a cotransfected CMV-SPAP plasmid as an internal control. Five genes (PRODH, DGCR14, GSTT2, SERPIND1, and a gene tentatively called DKFZP434P211) showed activity differences between haplotypes of greater than 1.5-fold. Of those, PRODH, which encodes proline dehydrogenase, has previously been highlighted in relation to schizophrenia, and the functional promoter polymorphism reported here may be involved in pathogenic mechanisms.

  18. Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis.

    PubMed

    Wu, Ming-Yue; Wu, Yang; Zhang, Yong; Liu, Cai-Yun; Deng, Chun-Yan; Peng, Le; Zhou, Lan

    2017-04-21

    Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I(2) = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I(2) = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I(2) = 0%). Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

  19. Serine/threonine kinase 15 gene polymorphism and risk of digestive system cancers: A meta-analysis.

    PubMed

    Luo, Jianfei; Yan, Ruicheng; Zou, Li

    2015-01-01

    Previous studies have reported an association between the two coding polymorphisms (91T>A and 169G>A) of the serine/threonine kinase 15 (STK15) gene and the risk of digestive system cancers; however, the results are inconsistent. In the present study, a meta-analysis was carried out to assess the association between the two STK15 polymorphisms and the risk of digestive system cancers. Relevant studies were identified using PubMed, Web of Science, China National Knowledge Infrastructure, WanFang and VIP databases up to February 18, 2014. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed or random effects model. A total of 15 case-control studies from 14 publications were included. Of these, 15 studies concerned the 91T>A polymorphism and included 7,619 cases and 7,196 controls and four studies concerned the 161G>A polymorphism and included 826 cases and 713 controls. A significantly increased risk of digestive system cancers was observed for the 91T>A polymorphism (recessive model: OR, 1.19; 95% CI, 1.07-1.31). In subgroup analysis by ethnicity, a significant association was detected in Asian populations (recessive model: OR, 1.21; 95% CI, 1.08-1.36) but not in Caucasian and mixed populations. Stratification by tumor type indicated that the 91T>A polymorphism was associated with an increased risk of esophageal and colorectal cancers under the recessive model (OR, 1.19; 95% CI, 1.03-1.38; and OR, 1.24; 95% CI, 1.04-1.46; respectively); however, no significant association was observed between the 169G>A polymorphism and the risk of digestive system cancers in any of the genetic models. Furthermore, in subgroup analysis by ethnicity, similar results were observed in the Asian and Caucasian populations. The present meta-analysis demonstrated that the STK15 gene 91T>A polymorphism, but not the 169G>A polymorphism, may be a risk factor for digestive system cancers, particularly for esophageal and colorectal cancers.

  20. Vascular endothelial growth factor gene polymorphisms and psoriasis susceptibility: a meta-analysis.

    PubMed

    Lee, Y H; Song, G G

    2015-11-19

    The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted to examine the associations between the +405 C/G, -460 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and psoriasis using allele contrast and recessive, dominant, and additive models. Seven studies on VEGF polymorphisms and psoriasis involving 1956 subjects (psoriasis patients 665, controls 1291) were included in this meta-analysis. We observed no association between psoriasis and the VEGF +405 C allele in all study subjects (odds ratio = 0.984, 95% confidence interval = 0.754-1.285, P = 0.906), but stratification by ethnicity indicated a significant association between the VEGF +405 C allele and psoriasis in Asians (odds ratio = 0.762, 95% confidence interval = 0.628-0.923, P = 0.005). In addition, we observed a significant association between the VEGF -460 C allele and psoriasis in Europeans (odds ratio = 0.807, 95% confidence interval = 0.672-0.968, P = 0.021). Meta-analyses of the -1154 A/G polymorphism also revealed a significant association with psoriasis in Europeans. However, the VEGF -2578 A/C polymorphism showed no association in all subjects or in Europeans or Asians. This meta-analysis suggests the VEGF +405 C/G polymorphism confers susceptibility to psoriasis in Asians, and that the -460 C/T and -1154 A/G polymorphisms confer susceptibility to psoriasis in Europeans.

  1. Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

    PubMed Central

    Wu, Jingjing; Liu, Zheng; Meng, Kai; Zhang, Ling

    2014-01-01

    Background Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults. Method Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis. Results A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I2 = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I2 = 51%). The susceptibility of obesity was increased based on genotypes of TTanalysis of different regions revealed that the ADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies (P

  2. Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease: Meta-Analysis.

    PubMed

    Jung, J H; Song, G G; Kim, J-H; Choi, S J

    2016-11-01

    The aim of this study was to perform a meta-analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta-analyses were conducted on the associations between AITD and the -1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta-analysis. This meta-analysis showed significant associations between IL10 at the -1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13-1.82, P = 0.003), but no association between the IL10 -592 C allele and the -819 C allele and AITD. Subgroup studies demonstrated significant associations between the -1082 G allele and susceptibility to Graves' disease. Ethnicity-specific meta-analysis revealed significant associations between the -1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta-analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00-1.36, P = 0.04). Meta-analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  3. Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis

    PubMed Central

    Li, Jingguang; Zhao, Yajun; Li, Rena; Broster, Lucas S.; Zhou, Chenglin; Yang, Suyong

    2015-01-01

    A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen’s d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen’s d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders. PMID:26121678

  4. Vascular endothelial growth factor gene polymorphisms and vasculitis susceptibility: A meta-analysis.

    PubMed

    Song, Gwan Gyu; Kim, Jae-Hoon; Lee, Young Ho

    2014-06-01

    The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis. Meta-analyses were conducted on the associations between the -634 C/G, +936 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and vasculitis. Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF -634 C allele (OR=1.161, 95% CI=0.921-1.464, p=0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF+936 T allele (OR=1.121, 95% CI=0.905-1.390, p=0.295). However, stratification by ethnicity indicated a significant association between the VEGF+936 T allele and vasculitis in Europeans, but not in Asians (OR=1.486, 95% CI=1.038-2.128, p=0.030; OR=0.958, 95% CI=0.773-1.253, p=0.755). Meta-analysis showed no association between vasculitis and the VEGF -1154 A/G and 2578 A/C polymorphisms. This meta-analysis suggests that the VEGF+936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  5. [Analysis of POU1F1 gene polymorphisms in Qinchuan cattle and Chinese Holstein cattle].

    PubMed

    Yan, Lin-Jun; Liu, Bo; Fang, Xin-Tang; Chen, Hong; Zhang, Run-Feng; Bao, Bin; Zhang, Hai-Jun

    2006-11-01

    PCR-RFLP was applied to analyze the polymorphisms of POU1F1 gene in 218 Qinchuan cattle (QQ) and Chinese Holstein cattle (HC). Results demonstrated Hinf I polymorphisms in the 451 bp PCR product in the two populations. The frequencies of alleles A/B in QQ and HC populations were 0.232/0.768 and 0.132/0.868, respectively. The frequencies of three genotypes AA, AB and BB were 0.030/0.403/0.567 and 0.007/0.251/0.742, respectively. Qinchuan cattle population was at Hardy-Weinberg equilibrium at this locus, but Chinese Holstein cattle population was not. The gene heterozygosity/effective allele gene number/Shannon information entropy/polymorphism information content of Qinchuan cattle and Chinese Holstein cattle populations were listed for 0.356/1.553/0.541/0.292 and 0.229/1.297/0.390/0.203, respectively. All indices were higher in the Qinchuan cattle population.

  6. Analysis of some polymorphic markers of the CFTR gene in cystic fibrosis patients and healthy donors from the Moscow region

    SciTech Connect

    Amosenko, F.A.; Sazonova, M.A.; Kapranov, N.I.; Trubnikova, I.S.; Kalinin, V.N.

    1995-04-01

    Allelic frequencies of three polymorphic markers in the CFTR gene were estimated on chromosomes derived from cystic fibrosis (CF) patients and healthy donors from Moscow and the Moscow region. These polymorphic markers are tetranucleotide tandem repeats GATT in intron 6B, M470V in exon 10, and T854T in exon 14 (fragment A). Frequencies at allele 1 of the M470V marker, along with allele 2 of GATT and T854T, are two times higher for CF patients without {Delta}F508 mutation than for healthy donors, and there is linkage disequilibrium of these alleles of the polymorphic markers analyzed with the CF gene. Allele 1 of M470V and T854T markers, as well as allele 2 of the GATT marker (six repeats), are absolutely linked to mutation F508 of the CFTR gene. Using the polymorphic markers studied, family analysis of CF was carried out in two families. 10 refs., 1 fig., 1 tab.

  7. Association between two interleukin-2 gene polymorphisms and cancer susceptibility: a meta-analysis

    PubMed Central

    Zhang, Meng; Tan, Xiuxiu; Huang, Junjie; Xie, Lijuan; Wang, Hao; Shi, Jizhou; Lu, Wei; Lv, Zhaojie; Mei, Hongbing; Liang, Chaozhao

    2016-01-01

    Background Several epidemiological studies have illustrated that polymorphisms in interleukin-2 (IL-2) were associated with diverse cancer types. However, recently published statistics were inconsistent and inconclusive. Therefore, the current meta-analysis was performed to elaborate the effects of IL-2 polymorphisms (rs2069762 and rs2069763) on cancer susceptibility. Material and methods A total of 5,601 cancer cases and 7,809 controls from 21 published case–control studies were enrolled in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between IL-2 polymorphisms and cancer susceptibility. Results Our study demonstrated an increased susceptibility to cancer in rs2069762 (G vs T: OR =1.268, 95% CI =1.113–1.445; GG vs TT: OR =1.801, 95% CI =1.289–2.516; GT vs TT: OR =1.250, 95% CI =1.061–1.473; GG + GT vs TT: OR =1.329, 95% CI =1.118–1.579; GG vs GT + TT: OR =1.536, 95% CI =1.162–2.030). In the subgroup analysis, increased susceptibility to cancer was identified in the hospital-based group and PHWE<0.05 (P-value of the Hardy–Weinberg equilibrium [HWE]) group. In addition, a positive association with cancer susceptibility was observed among both Chinese and non-Chinese. However, no relationship was detected between the rs2069763 polymorphism of IL-2 and cancer susceptibility. Conclusion To conclude, rs2069762 polymorphism of IL-2 contributed to an increased susceptibility to cancer, whereas no association was identified between rs2069763 polymorphism and cancer susceptibility. Further detailed studies are warranted to confirm our findings. PMID:27143914

  8. Association between IL-10 Gene Polymorphisms and Susceptibility of Tuberculosis: Evidence Based on a Meta-Analysis

    PubMed Central

    Liang, Bin; Guo, Yang; Li, Yunhui; Kong, Hong

    2014-01-01

    Background A number of observational studies have been conducted to investigate the association of IL-10 gene polymorphisms with tuberculosis (TB) susceptibility. However, the results of different studies were inconsistent. The aim of this study was to investigate the relationship between IL-10 -1082G/A, -819T/C, and -592A/C polymorphisms and TB risk by meta-analysis. Methods A literature search was conducted among six English databases (PubMed, Embase, Web of Science, Science Direct, SpringerLink and EBSCO) and two Chinese databases (Wanfang and Chinese National Knowledge Infrastructure databases) to identify studies involving association between IL-10 −1082G/A, −819T/C, and −592A/C polymorphisms and TB susceptibility before May. 2013. Statistical analysis was performed using Revman 5.0 and Stata 12.0. Results A total of 31 studies with 6,559 cases and 7,768 controls were included in this meta-analysis. The results showed that three polymorphisms (-1082G/A, -819T/C, and -592A/C) in the IL-10 gene were not associated with the risk of TB in general population. In the subgroup analysis by ethnicity, IL-10 -1082G/A polymorphism was associated with TB risk in Europeans (AA+AG vs. GG: OR =  0.57, 95% CI = 0. 0.37–0.89, P = 0.01) and Americans (AA+AG vs. GG: OR =  0.39, 95% CI = 0.27–0.57, P<0.01), and IL-10 -819T/C (C allele vs. T allele: OR = 0.83, 95% CI = 0.72–0.96, P = 0.01) and -592A/C (CC+AC vs. AA: OR =  0.65, 95% CI = 0.49–0.85, P = 0.002) polymorphisms were significantly associated with TB risk in Asians. Conclusion This meta-analysis provides strong evidence that IL-10-1082G/A polymorphism was associated with TB risk in Europeans and Americans, and IL-10 -819T/C and -592A/C polymorphisms could be risk factors for TB in Asians. Additional well designed large studies were required for the validation of our results. PMID:24523896

  9. Two polymorphisms in the Fractalkine receptor CX3CR1 gene influence the development of atherosclerosis: a meta-analysis.

    PubMed

    Wu, Jian; Yin, Rui-Xing; Lin, Quan-Zhen; Guo, Tao; Shi, Guang-Yuan; Sun, Jia-Qi; Shen, Shao-Wen; Li, Qing

    2014-01-01

    The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis.

  10. Association of AGTR1 gene A1166C polymorphism with the risk of heart failure: a meta-analysis.

    PubMed

    Zhang, J A; Li, J R; Qiao, Y J

    2015-08-07

    The aim of this study was to investigate the correlation between the A1166C polymorphism in the angiotensin II type 1 receptor (AT1R) gene and heart failure (HF) risk using meta‑analysis. The PubMed database was searched, and data were extracted independently by two reviewers. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. Statistical analysis was performed using the STATA 12.0 software. The results of the meta‑analysis showed no significant association between the AT1R A1166C polymorphism and HF risk (AA vs CC: OR = 0.72, 95%CI = 0.31-1.68; AA vs AC: OR = 0.78, 95%CI = 0.52-1.18; dominant model: OR = 1.37, 95%CI = 0.92-2.04; recessive model: OR = 0.73, 95%CI = 0.30-1.75). In the subgroup analysis by ethnicity, the results also showed no significant association between A1166C polymorphism and susceptibility to HF in both Caucasian and Asian populations. In conclusion, this meta-analysis suggests that the A1166C polymorphism in AT1R may not be associated with susceptibility to HF. Further large and well-designed studies are needed to confirm these conclusions.

  11. Phylogenetic reconstruction and polymorphism analysis of BK virus VP2 gene isolated from renal transplant recipients in China

    PubMed Central

    WANG, ZHANG-YANG; HONG, WEI-LONG; ZHU, ZHE-HUI; CHEN, YUN-HAO; YE, WEN-LE; CHU, GUANG-YU; LI, JIA-LIN; CHEN, BI-CHENG; XIA, PENG

    2015-01-01

    BK polyomavirus (BKV) is important pathogen for kidney transplant recipients, as it is frequently re-activated, leading to nephropathy. The aim of this study was to investigate the phylogenetic reconstruction and polymorphism of the VP2 gene in BKV isolated from Chinese kidney transplant recipients. Phylogenetic analysis was carried out in the VP2 region from 135 BKV-positive samples and 28 reference strains retrieved from GenBank. The unweighted pair-group method with arithmetic mean (UPGMA) grouped all strains into subtypes, but failed to subdivide strains into subgroups. Among the plasma and urine samples, all plasma (23/23) and 82 urine samples (82/95) were identified to contain subtype I; the other 10 urine samples contained subtype IV. A 86-bp fragment was identified as a highly conserved sequence. Following alignment with 36 published BKV sequences from China, 92 sites of polymorphism were identified, including 11 single nucleotide polymorphisms (SNPs) prevalent in Chinese individuals and 30 SNPs that were specific to the two predominant subtypes I and IV. The limitations of the VP2 gene segment in subgrouping were confirmed by phylogenetic analysis. The conserved sequence and polymorphism identified in this study may be helpful in the detection and genotyping of BKV. PMID:26640547

  12. The association between HDAC9 gene polymorphisms and stroke risk in the Chinese population: A meta-analysis

    PubMed Central

    Zhou, Xin; Guan, Tangming; Li, Shuyuan; Jiao, Zinan; Lu, Xiaoshuang; Huang, Xiaodi; Ji, Yuhua; Ji, Qiuhong

    2017-01-01

    Several recent genome-wide association studies (GWASs) have suggested that the histone deacetylase 9 (HDAC9) gene is associated with stroke, but the reliability of these findings remains controversial, particularly for the data derived from different ethnicities and geographical locations. Therefore, we performed a meta-analysis to explore the associations between HDAC9 polymorphisms and the risk of stroke in the Chinese population. All eligible case-control studies that met the search criteria were retrieved from multiple databases, and six case-control studies with a total of 2,356 stroke patients and 3,420 healthy controls were included. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations of 3 HDAC9 gene polymorphisms with stroke risk. Our results revealed statistically significant associations of the rs2107595 (T/C) polymorphism with an increased risk of stroke in the allele, codominant and dominant models. Additionally, the rs2389995 (G/A) polymorphism was found to be significantly associated with a decreased risk of stroke in all genetic models. In conclusion, this meta-analysis suggested that the T allele of rs2107595 in HDAC9 increases the risk of stroke but that the G allele of rs2389995 decreases the risk of stroke in the Chinese population. PMID:28145521

  13. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy.

    PubMed

    Luo, Shasha; Wang, Furu; Shi, Chao; Wu, Zhifeng

    2016-08-10

    To shed light on the conflicting findings of the association between the methylenetetrahydrofolate reductase gene (MTHFR) 677C/T polymorphism and the risk of diabetic retinopathy (DR), a meta-analysis was conducted. A predefined search was performed on 1747 DR cases and 3146 controls from 18 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the sizes of overall and stratification effects of the MTHFR 677C/T polymorphism on the risk of DR, as appropriate. Risks were evaluated by odds ratios (OR) with 95% confidence intervals (95% CI). We found a significant association between the MTHFR 677C/T polymorphism and the risk of DR for each genetic model (recessive model: OR = 1.67; 95% CI: 1.19-2.40 and dominant model: OR = 1.71; 95% CI: 1.28-2.28; respectively). In stratified analysis; we further found that the Asian group with both types of diabetes mellitus (DM) showed a significant association with genetic models (recessive model: OR = 2.16; 95% CI: 1.75-2.60 and dominant model: OR = 1.98; 95% CI: 1.42-2.76; respectively). Our study suggested that the MTHFR 677C/T polymorphism may contribute to DR development, especially in Asian populations. Prospective and additional genome-wide association studies (GWAS) are needed to clarify the real role of the MTHFR gene in determining susceptibility to DR.

  14. Methylenetetrahydrofolate reductase gene polymorphism in endometrial cancer: A systematic review and meta-analysis.

    PubMed

    Wang, Xian-Jun; Xu, Li-Hui; Chen, Yue-Ming; Luo, Li; Tu, Qiao-Feng; Mei, Jin

    2015-10-01

    We conducted a meta-analysis of case-controlled prospective or retrospective studies to assess the effect of MTHFR polymorphisms on the risk of developing endometrial cancer. PubMed, Cochrane, EMBASE, and ISI Web of Knowledge were searched (up to March 2014) for prospective or retrospective case-controlled studies that investigated the association of three MTHFR polymorphisms (rs180113 [C677T], rs1801131 [A1289C], and rs2274976 [G1793A]) with endometrial cancer. The patient population included subjects from three separate countries: China, Spain, and the USA. Only one study reported quantitative findings for MTHFR G1793A and, consequently, this polymorphism was not evaluated in our analysis. There were no significant associations of any MTHFR C677T or MTHFR A1298C alleles or genotypes with endometrial cancer (all p > 0.300). This meta-analysis does not support the association of endometrial cancer with two common MTHFR polymorphisms from this patient population. Copyright © 2015. Published by Elsevier B.V.

  15. Association analysis of heat shock protein 70 gene polymorphisms in schizophrenia.

    PubMed

    Kim, Jung Jin; Mandelli, Laura; Lim, Suzy; Lim, Hyun Kook; Kwon, Oh Joo; Pae, Chi Un; Serretti, Alessandro; Nimgaonkar, Vishwajit L; Paik, In-Ho; Jun, Tae-Youn

    2008-06-01

    Heat shock proteins (HSPs) are a promising candidate gene in schizophrenia as they are believed to play a protective role in the central nervous system. An alteration in the titers of antibodies to the HSPs in schizophrenia patients has been suggested. Association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B) and schizophrenia has been reported. Therefore, this study investigated the association between an enlarged set of SNPs at HSP70 gene and schizophrenia. Two hundred and ninety-four patients with schizophrenia and 287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70 were performed using pyrosequencing method. Haploview 3.2 was used to generate a linkage disequilibrium map and to test for Hardy-Weinberg equilibrium. Single locus and haplotype-based associations were tested. Tests for associations using and multi-marker haplotypes were performed by using a COCAPHASE v2.403. Association of SNP markers and clinical variables were analyzed by analysis of variance. Significant association was detected at rs2075799 (allele A, X2 = 8.03, df = 1, P = 0.0046), but not at rs2227956 (P = 0.28), rs1043618 (P = 0.88), rs562047 (P = 0.47) or rs539689 (P = 0.32). In fact, the rs2075799*G/A genotype was more represented in patients with schizophrenia than in controls (X2 = 8.23, df= 1, P = 0.0041). Haplotype based associations were also detected (global P value 0.000003); the T-A-C-C-G haplotype was more prevalent among the patients (odds ratio, OR 5.95). Sliding windows analysis revealed a major contribution from rs2227956 and rs2075799 (global-P value 0.0075), with T-A haplotype significantly associated with schizophrenia. There was no evidence of an association between the clinical variables and schizophrenia across the genotypes. Our results raise the possibility that HSP70 gene (i.e., haplotypes of rs2075799) might be implicated in the development of schizophrenia, although limited by rare haplotypic

  16. Analysis of population genetic structure from Bucaramanga (Colombia) based on gene polymorphisms associated with the regulation of blood pressure

    PubMed Central

    Rondón, Fernando; Vargas, Clara Inés; Oróstegui, Myriam; Bautista, Leonelo; Serrano, Norma Cecilia; Páez, María c; Castillo, Adriana

    2012-01-01

    Introduction: In spite of nearly 40% of variability in blood pressure being explained by genetic factors, the identification of genes associated with essential high blood pressure is difficult to determine in populations where individuals have different genetic backgrounds. In these circumstances it is necessary to determinate whether the population is sub-structured because this can bias studies associated with this disease. Objective: To determine the genetic structure of the population in Bucaramanga from genetic polymorphisms associated with the regulation of blood pressure: 448G>T, 679C>T y 1711C>T from the gene kinase 4 of the dopaminergic receptor linked to the protein G and Glu298Asp, -786T>C and the VNTR of the intron 4 of the gene of endothelial nitric oxide. Methods: A sample of 552 unrelated individuals was studied through analysis of restriction fragment length polymorphism. The allelic, haplotypic and genotypic frequencies were calculated, the Hardy-Weinberg equilibrium was determined and a molecular analysis of variance was performed to determine the genetic structure. Results: Thirty-eight (38) Haplotypes were identified with GCCTG4b being the most frequent (21.2%). The most diverse polymorphism was 448G>T with a frequency of 49.9% for heterozygous. The six polymorphisms were found in genetic equilibrium and a genetic structure of populations was not evidenced (FST= 0.0038). Conclusion: The population studied does not present a genetic sub-structure and the polymorphisms analyzed were found in genetic equilibrium. This indicates that the population mixes randomly and there are no sub-groups capable of affecting the results of the association studies. PMID:24893057

  17. Association analysis of DISC1 gene polymorphisms with Attention-Deficit Hyperactivity Disorder in Iranian population.

    PubMed

    Kayyal, Matin; Movafagh, Abolfazl; Hashemi, Mehrdad; Sayad, Arezou; Emamalizadeh, Babak; PourIran, Khashayar; Kayyal, Mohammadmoien; Amirabadi, Mohammad Reza Eslami; Zamani, Mahdi; Darvish, Hossein

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. In this research work, for the first time, we investigated the association of three SNPs (rs11122330, rs6675281 and rs11122319) in the DISC1 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. (P value = 0.008, OR= 1.5837, 95% CI= 1.1012 to 2.2776). Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world.

  18. [Analysis of TRPV1 gene polymorphisms in Spanish patients with neuropathic pain].

    PubMed

    Armero, Pilar; Muriel, Clemente; López, Mónica; Santos, Juan; González-Sarmiento, Rogelio

    2012-06-02

    The vanilloid receptor TRPV1 is a molecular integrator of painful stimuli. Several recent studies suggest that TRPV1 may play a role in development and maintenance of chronic pain. In an attempt to determine if genotypic variations in TRPV1 gene could be involved in the susceptibility to suffer neuropathic pain we have studied genetic variants of human TRPV1 gene. We have studied the distribution of Met315Ile and Ile585Val TRPV1 polymorphisms in a total of 440 Caucasian subjects: 232 patients with neuropathic pain and 208 healthy subjects matched by age and sex. The polymorphisms were analyzed with polymerase chain reaction (PCR) using TaqMan probes specific for each allele. Our results show that the distribution of Met315Ile and Ile585Val genotypes and alleles is similar in patients with neuropathic pain and in healthy subjects. However, the Met315Met genotype is more frequent in females diagnosed as suffering neuropathic pain. No differences were observed when we segregate the patients according to visual analogue scale values. The observation of differences in the distribution of Met315Ile TRPV1 genotypes only in females diagnosed of neuropathic pain suggests that this polymorphism, together with other physiological factors such as sex, may influence individual susceptibility to neuropathic pain. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  19. The catalase C-262T gene polymorphism and cancer risk: a systematic review and meta-analysis.

    PubMed

    Shen, Yongchun; Li, Diandian; Tian, Panwen; Shen, Konglong; Zhu, Jing; Feng, Mei; Wan, Chun; Yang, Ting; Chen, Lei; Wen, Fuqiang

    2015-04-01

    Many studies suggest that catalase C-262T gene polymorphism is associated with cancer risk, but with inconsistent results. This study aimed to summarize the overall association between catalase C-262T polymorphism and cancer risk. Literature search was performed in PubMed, Embase, and other databases, studies regarding the association between catalase C-262T polymorphism and cancer risk were identified, and data were retrieved and analyzed by using Review Manager 5.0.24 and STATA 12.0. A total of 18 publications with 22 case-control studies, including 9777 cancer patients and 12,223 controls, met the inclusion criteria. Meta-analysis results showed significant association between catalase C-262 T polymorphism and cancer risk (TT vs CT + CC: odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.31, P = 0.01). Subgroup analyses stratified by cancer types suggested the catalase C-262T polymorphism was significantly associated with an increased prostate cancer risk (TT vs CT + CC: OR = 1.61, 95% CI = 1.17-2.22, P = 0.004); for subgroup analyses stratified by ethnicity, no associations between this polymorphism and Asians or whites were identified (CT + TT vs CC: OR = 1.11, 95% CI = 0.98-1.26, P = 0.09 for whites; OR = 1.19, 95% CI = 0.78-1.80, P = 0.42 for Asians). In summary, the catalase C-262T polymorphism may be a risk factor for cancer with cancer type-specific effects. Further studies should be performed to confirm these findings.

  20. [ANALYSIS OF THE ASSOCIATION BETWEEN THR83ALA POLYMORPHISM OF MATRIX GLA-PROTEIN GENE AND LOWER EXTREMITY ARTERIAL CALCIFICATION].

    PubMed

    Ataman, Yu; Еrmolenko, Т; Grek, A; Zharkova, A; Ovechkin, D

    2016-03-01

    Lower extremity arterial calcification (AC) is a common pathological process that has independent significance in the pathogenesis of many cardiovascular diseases. There is evidence that development of AC associated with Thr83Ala polymorphism of matrix GLA-protein gene. The objective of this study was to examine the association between Thr83Ala polymorphism of matrix Cla protein (MGP) gene and AC in male and female subjects of the Ukrainian population. 40 AC and 40 healthy controls were recruited to the study. MGP exon 4 Thr83Ala polymorphism (rs 4236) was examined using the polymerase chain reaction with subsequent restriction fragment length polymorphism analysis. The obtained data show that the substitution of threonin by alanine at position 83 in a molecule of MGP can affect its functional characteristics and anticalcinogenic properties. The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of Thr83Ala polymorphism in patients with AC was 40,0%, 47,5%, and 12,5% respectively. The corresponding distribution of variants in the control group was 32,5%, 42,5% and 25,0% (p=0,352 by χ2 -test). In women who are carriers of Ala/Ala-variant, CA occurs more rarely than in men with the same genotype (p=0,036 by χ2 -test). The substitution of threonine by alanine due to MGP exon 4 Thr83Ala polymorphism is related to a decrease in the likelihood of CA in female persons in the Ukrainian population.

  1. Analysis of the genetic effects of CAPN1 gene polymorphisms on chicken meat tenderness.

    PubMed

    Shu, J T; Zhang, M; Shan, Y J; Xu, W J; Chen, K W; Li, H F

    2015-02-13

    The micromolar calcium-activated neutral protease gene (CAPN1) is a physiological candidate gene for meat tenderness. Four previously identified single nucleotide polymorphism (SNP) markers located within the CAPN1 gene were evaluated for their associations with variation in the meat tenderness of a Chinese indigenous chicken breed, a higher meat quality breed (i.e., Qingyuan partridge chicken), and the commercial Recessive White chicken breed. Warner-Bratzler shear force measurements were used to determine tenderness phenotypes for all animals; intramuscular fat (IMF) content and rate of water loss in the breast muscles were also measured. Genotyping was performed by the polymerase chain reaction-ligase detection reaction method. Polymorphisms were identified for all markers, except CAPN1 2546. The frequency of allele T was zero, and allele C was fixed for CAPN1 2546 in the studied populations. The SNP CAPN1 3535 in the CAPN1 gene was significantly associated with tenderness and other meat quality traits, where animals inheriting the AA genotype had smaller shear force values, lower water loss rates, and higher IMF contents. Moreover, H1 (AAA) was the most advantageous haplotype for meat tenderness. The results of this study confirm some previously documented associations. Furthermore, novel associations have been identified that, following validation in other populations, could be incorporated into breeding programs to improve meat quality.

  2. A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal localization in Chinese raccoon dog and Arctic fox.

    PubMed

    Skorczyk, Anna; Flisikowski, Krzysztof; Switonski, Marek

    2012-05-01

    Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are responsible for monogenic obesity, and some of them appear to be associated with predisposition or resistance to polygenic obesity. Thus, this gene is considered a functional candidate for fat tissue accumulation and body weight in domestic mammals. The aim of the study was comparative analysis of chromosome localization, nucleotide sequence, and polymorphism of the MC4R gene in two farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms. In the Chinese raccoon dog, only one silent substitution in the coding sequence was identified; whereas in the arctic fox, four InDels and two single-nucleotide polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9 (NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are discussed in terms of genome evolution of species belonging to the family Canidae and their potential use in animal breeding.

  3. Association between FTO gene polymorphism (rs9939609 T/A) and cancer risk: a meta-analysis.

    PubMed

    Huang, Xiaoyi; Zhao, Jian; Yang, Mingyuan; Li, Ming; Zheng, Jianming

    2017-09-01

    Obesity is a risk factor of cancer. Several genes have been found to play an important role in aetiology of obesity and tumourigenesis. Recently, some studies suggested that rs9939609 polymorphism might be significantly associated with cancer risk, while the results of some other studies were controversial. Databases with time limitation from January 1984 to April 2015 were searched. The pooled odds ratio (OR) with 95% confidence interval was calculated to assess the associations, and subgroup meta-analyses were performed according to the type of cancer and ethnicity of the study populations. Overall, the significant association between rs9939609 polymorphism and cancer risk was found in homozygote model and recessive model. As to subgroup classified by cancer type, there was significant association in endometrial cancer and pancreatic cancer, while no statistical significance was detected in other kind of cancers. Besides, in the subgroup analysis of ethnicity, our results indicated that rs9939609 polymorphism was significantly associated with cancer risk in Asians. The rs9939609 polymorphism may be involved the susceptibility of endometrial cancer and pancreatic cancer, especially in Asian populations. Thus, rs9939609 may be a potential biomarker in early diagnosis or gene therapy target of endometrial cancer and pancreatic cancer. © 2016 John Wiley & Sons Ltd.

  4. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    PubMed Central

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  5. Association between the methylenetetrahydrofolate reductase gene C677T polymorphism and sudden sensorineural hearing loss: a meta-analysis.

    PubMed

    Shu, Jingcheng; Yin, Shihua; Tan, An-Zhou; He, Meirong

    2015-09-01

    A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and sudden sensorineural hearing loss (SSNHL), but the results were inconsistent. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with SSNHL. A systematic literature search of the associated studies up to May 1, 2014, was conducted using the following electronic databases: PubMed, Embase, Medline, and the China National Knowledge Infrastructure. Statistical analyses were performed by STATA12.0 software, with odds ratios (ORs) and their 95 % confidence intervals (CIs). Six eligible studies including covering 1,271 objects were identified. A pooled analysis of these studies showed no significant association between C677T polymorphism and risk of SSNHL: T vs. C (OR = 1.334, POR = 0.105); TT vs. CC (OR = 1.580, POR = 0.231); CT vs. CC (OR = 1.500, POR = 0.123); TT vs. CC + CT (OR = 1.326, POR = 0.293); and TT + CT vs. CC (OR = 1.540, POR = 0.102). But in subgroup analysis, a significant association was found in European populations (T vs. C, OR = 1.542, 95 % CI 1.008-2.359, P = 0.046; TT vs. CT + CC, OR = 1.856, 95 % CI 1.245-2.767, P = 0.002). There was no significant association in any model in the Asian populations. The present meta-analysis suggests that MTHFR gene C677T polymorphism is significantly associated with increased risk of SSNHL disease in European populations, but no statistically significant association was found between the MTHFR C677T gene mutation and SSNHL in Asian. Further large and well-designed studies are needed to confirm this association.

  6. Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin

    PubMed Central

    Kapur, Suman; Mehra, Shipra; Gajjar, Devarshi; Vasavada, Abhay; Kapoor, Manav; Sharad, Shashwat; Alapure, Bhagwat; Rajkumar, S

    2009-01-01

    Aim: Polymorphisms in γ-crystallins (CRYG) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA/CRYGB genes in control subjects of western Indian origin. Materials and Methods: A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes. Results: The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly (P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene. Conclusions: This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract. PMID:19384013

  7. Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis.

    PubMed

    Yadav, Upendra; Kumar, Pradeep; Gupta, Sanjay; Rai, Vandana

    2016-04-01

    Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was reported as risk factor for congenital defects, metabolic and neuropsychiatric disorders. Numerous case-control studies investigated C677T polymorphism as risk factor for schizophrenia but results of these studies were contradictory. To draw a conclusion, a meta-analysis of all available case-control studies was performed. PubMed, Google Scholar, Springer Link and Elsevier databases were searched for eligible case-control studies. Pooled odds ratio with 95%CI was used as an association measure and all statistical analyses were performed by Open Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372 controls were included in the present meta-analysis. Results of meta-analysis showed significant associated between C677T polymorphism and risk of schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04-1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19, 95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses. Subgroup analysis was done according to ethnicity and significant association was found between C677T polymorphism and risk of schizophrenia in all three ethnic populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21; 95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In conclusion the results of the present meta-analysis suggested that the MTHFR C677T polymorphism is a risk factor for schizophrenia.

  8. Polymorphism analysis in genes of the somatotropic axis in Nellore cattle selected for growth.

    PubMed

    Cardoso, Diercles Francisco; de Souza, Fábio Ricardo Pablos; de Camargo, Gregório Miguel Ferreira; Fonseca, Patrícia Dias da Silva; Fonseca, Larissa Fernanda Simielli; Braz, Camila Urbano; Boligon, Arione Augusti; Mercadante, Maria Eugênia Zerlotti; de Albuquerque, Lucia Galvão; Tonhati, Humberto

    2014-07-25

    The somatotropic axis consists of genes that are involved in muscular development. These genes are potential regions of study to identify possible QTL for economically important traits in beef cattle. The aim of this study was to verify the existence of GH1, POU1F1, and GHR polymorphisms in Nellore cattle to verify the influence of selection in these mutations and to analyse the association between molecular markers and body weight at different ages, yearling hip height, carcass fat thickness and loin eye area. Six hundred forty-five animals from the Centro APTA Bovinos de Corte, were genotyped by PCR-RFLP techniques. The association analyses were performed with general mixed models taking into consideration the effect of one marker, and other model taking into consideration interactions between two molecular markers. Only the molecular markers rs81109601 on GH1 and rs109136815 on GHR were polymorphic; however, they were not found to be under selection. The association of the GHR rs109136815 marker and loin eye area was observed (p<0.05), as well as the effect of interaction between the markers and the female body weight at 550 days of age (p<0.04). The interaction effect should be considered in situations where the interactivity between two genes is known.

  9. Impact of gamma-glutamyl carboxylase gene polymorphisms on warfarin dose requirement: a systematic review and meta-analysis.

    PubMed

    Sun, Yifan; Wu, Zhitong; Li, Shan; Qin, Xue; Li, Taijie; Xie, Li; Deng, Yan; Chen, Junqing

    2015-04-01

    The Gamma-glutamyl carboxylase (GGCX) gene, as with Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), CytochromeP450 Complex Subunit 14 F2 (CYP4F2) and CytochromeP450 Complex Subunit2C9 (CYP2C9), is a candidate predictor for appropriate maintenance warfarin dose. However, the association between GGCX gene polymorphisms and warfarin dose requirement is still controversial. To quantify the influence of GGCX polymorphisms on warfarin dose requirements, we performed a systematic review and meta-analysis. According to PRISRM statement (Preferred reporting items for systematic reviews and meta-analyses), a comprehensive literature search was undertaken through August 2014 looking for eligible studies in Embase, Pubmed,Web of Science and the Cochrane Library. The impact of GGCX polymorphisms on mean daily warfarin dose (MDWD) was counted by means of Z test. RevMan 5.2.7 software (developed by the Cochrane Collaboration) was applied to analyze the relationship between GGCX gene polymorphisms and warfarin dose requirements. Nineteen articles including 21 studies with a total of 6957 patients were included in the meta-analysis. Among three investigated single nucleotide polymorphisms (SNPs), rs11676382 showed higher CC genotype frequencies in Asian than those in Caucasian (97.7% vs. 86.9%); patients who were "G carriers" (that is, carried the GGCX rs11676382 CG or GG genotypes) required 27% lower warfarin dose than CC genotype [95%Confidence Interval (CI)=17%-37%, P=0.000, I(2)%=82.0 and PQ=0.000], moreover, stratified analysis by ethnicity showed similar results in Caucasian (23% lower, 95%CI=12%-33%), but not in Asian. With respect to genetic variation of rs699664 and rs121714145 SNPs, no significant impact on warfarin dose requirements were demonstrated. This meta-analysis suggested that GGCX rs11676382 polymorphism may be one of factors affecting the dose of warfarin requirement, and the effects are different in different ethnicities. Further studies about this

  10. Lack of association between DRD2 Taq1A gene polymorphism and smoking cessation therapy: a meta-analysis.

    PubMed

    Choi, Hye Duck; Shin, Wan Gyoon

    2015-06-01

    Recent studies have reported that genetic factors are significantly associated with smoking behavior, but the influence of the smoking behavior-related genes on smoking cessation treatment is still not clear. We analyzed the smoking cessation outcomes among previously reported studies involving participants who underwent smoking cessation therapy by comparing the following DRD2 Taq1A gene polymorphism using meta-analysis. In total, nine studies including 2,851 participants were assessed and the A1 allele carriers and A2 homozygotes were compared with respect to smoking cessation outcomes by meta-analysis. No significant association was observed for the main analysis (OR = 0.900; 95% CI, 0.751 - 1.078). In subgroup analysis, three studies were assessed by comparing participants with the A1/A1, A1/A2, and A2/A2 genotypes. A significant association between the DRD2 Taq1A polymorphism and< smoking cessation therapy was observed between the A1/A1 and A1/A2 genotypes (OR = 2.967; 95% CI 1.737 - 5.068) and between the A1/A2 and A2/A2 genotypes (OR = 0.547; 95% CI 0.392 - 0.762), but not between the A1/A1 and A2/A2 genotypes (OR = 1.269; 95% CI 0.746 - 2.157). This study is the first meta-analysis to evaluate and quantitatively integrate the association between the DRD2 Taq1A polymorphism and smoking cessation therapy. A significant relationship between DRD2 Taq1A polymorphism and smoking cessation therapy was not observed.

  11. Polymorphism in regulatory gene sequences

    PubMed Central

    Mitchison, N A

    2001-01-01

    The extensive polymorphism revealed in non-coding gene-regulatory sequences, particularly in the immune system, suggests that this type of genetic variation is functionally and evolutionarily far more important than has been suspected, and provides a lead to new therapeutic strategies. PMID:11178274

  12. Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis.

    PubMed

    Lee, Young Ho; Song, Gwan Gyu

    2012-09-01

    The aim of this study was to determine whether the tumor necrosis factor-alpha-inducible protein 3 (TNFAIP3) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. The authors conducted meta-analyses on associations between the TNFAIP3 polymorphisms and SLE susceptibility, using fixed and random effects models. A total of eight comparative studies were included in this meta-analysis, which included four Asian, three European, and one African American population. Meta-analysis revealed that an association was found between the minor allele of rs2230926 and SLE in all subjects (odds ratio [OR] 1.848, 95% confidence interval [CI] 1.547-2.208, p<1.0×10(-9)). After stratification by ethnicity, the minor allele of rs2230926 was found to be significantly associated with SLE in Asians and Europeans (OR 1.821, 95% CI 1.495-2.219, p<1.0×10(-9); OR 2.251, 95% CI 1.830-2.768, p<1.0×10(-9)). In addition, a significant association was found between the minor allele of the rs5029939 polymorphism and the risk of developing SLE in all study subjects and Europeans (OR 1.804, 95% CI 1.255-2.592, p=0.001; OR 2.145, 95% CI 1.731-2.658, p<1.0×10(-9)). Furthermore, an association was found between the minor allele of rs3757173 and SLE in all study subjects (OR 1.540, 95% CI 1.017-2.331, p=0.041). However, no association was found between SLE susceptibility and rs6922466 (OR 0.953, 95% CI 0.812-1.120, p=0.561). This meta-analysis confirms that the TNFAIP3 polymorphisms are associated with SLE susceptibility in different ethnic groups, namely in Asians and Europeans.

  13. Association of rs2233678 and rs2233679 polymorphisms in the PIN1 gene with cancer risk: a meta-analysis.

    PubMed

    Zhenzhen, Li; Ning, Sun; Xianghua, Liu

    2014-01-01

    To data, epidemiological studies have assessed the association between peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene polymorphisms and cancer risk, including breast cancer, hepatocellular carcinoma, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, and laryngeal squamous cell cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs2233678 and rs2233679) of PIN1 gene and cancer risk by conducting a meta-analysis of case-control studies. A total of seven publications were included in this meta-analysis for both rs2233678 and rs2233679. Overall, rs2233678 polymorphism was found to be associated with decreased cancer risk in four genetic models (C-allele vs. G-allele: odd ratio (OR) = 0.73, 95% confidence interval (CI): 0.60-0.88; CC vs. GG: OR = 0.55, 95% CI: 0.36-0.84; CC+CG vs. GG: OR = 0.72, 95% CI 0.58-0.90; CC vs. CG+GG: OR = 0.58, 95% CI 0.38-0.89). However, the rs2233679 polymorphism of PIN1 gene did not appear to have an influence on caner susceptibility. In the subgroup analysis by cancer type, we observed that the PIN1 rs2233678 polymorphism was significantly associated with decreased breast cancer risk (C-allele vs. G-allele: OR = 0.73, 95% CI: 0.60-0.89; CC+CG vs. GG: OR = 0.71, 95% CI 0.57-0.89). Further subgroup analyses showed that the PIN1 rs2233678 polymorphism was associated with decreased cancer risk among Asian people (C-allele vs. G-allele: OR = 0.63, 95% CI: 0.51-0.79; CC vs. GG: OR = 0.44, 95% CI: 0.25-0.80; CC+CG vs. GG: OR = 0.63, 95% CI 0.50-0.79; CC vs. CG+GG: OR = 0.47, 95% CI 0.26-0.86). In conclusion, PIN1 rs2233678 polymorphism might be a potential biomarker for cancer risk among Asians, especially for breast cancer. Further large and well-designed studies are needed to confirm this conclusion.

  14. Association of Transforming Growth Factor Beta-1-509C/T Gene Polymorphism with Ischemic Stroke: A Meta Analysis

    PubMed Central

    Kumar, Pradeep; Kumar, Amit; Srivastava, Mukesh Kumar; Misra, Shubham; Pandit, Awadh Kishor; Prasad, Kameshwar

    2016-01-01

    Introduction: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS. Methods: A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests. Results: A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86). Conclusion: This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings. PMID:27303603

  15. Association between polymorphisms in ERCC2 gene and oral cancer risk: evidence from a meta-analysis.

    PubMed

    Zhang, Enjiao; Cui, Zhigang; Xu, Zhongfei; Duan, Weiyi; Huang, Shaohui; Tan, Xuexin; Yin, Zhihua; Sun, Changfu; Lu, Li

    2013-12-12

    Excision repair cross-complementing group 2 (ERCC2) plays important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of ERCC2 gene are suspected to influence the risks of oral cancer. We performed a meta-analysis to systematically summarize the possible association of ERCC2 rs1799793 and rs13181 polymorphisms with oral cancer risks. We retrieved the relevant articles from PubMed and Embase databases. Studies were selected using specific criteria. ORs and 95% CIs were calculated to assess the association. All analyses were performed using the Stata software. Six studies were included in this meta-analysis. There were no significant associations between ERCC2 rs1799793 and rs13181 polymorphism with overall oral cancer risk. In the stratified analysis by ethnicity, no significant associations were found. In the stratified analysis by tumor type, the risk of oral leukoplakia was significant associated with rs13181 polymorphism (AC vs. AA: OR = 1.28, 95% CI = 1.01-1.62, P = 0.546 for heterogeneity, I² = 0.0%; CC vs. AA: OR = 1.94, 95% CI = 0.99-3.79, P = 0.057 for heterogeneity, I² = 60.1%; dominant model AC + CC vs. AA: OR = 1.35, 95% CI = 1.08-1.69, P = 0.303 for heterogeneity, I² = 17.6%; allele C vs. A: OR = 1.38, 95% CI = 1.04-1.82. P = 0.043 for heterogeneity, I² = 56.4%). Rs13181 in ERCC2 gene might be associated with oral leukoplakia risk.

  16. Relationship between iris constitution analysis and TNF-alpha gene polymorphism in hypertensives.

    PubMed

    Yoo, Chun-Sang; Hwang, Woo-Jun; Hong, Seung-Heon; Lee, Hye-Jung; Jeong, Hyun-Ja; Kim, Su-Jin; Kim, Hyung-Min; Um, Jae-Young

    2007-01-01

    Iridology is a complementary and alternative medicine that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong hereditary component. Tumor necrosis factor-alpha (TNFalpha), a pleiotropic cytokine, has been implicated in many pathological processes including hypertension. In this paper, the relationship between iris constitution and TNFalpha gene polymorphism in those with hypertension is investigated. Eighty seven hypertensive individuals and 79 controls were classified according to iris constitution and the TNFalpha genotype of each individual determined. Compared to the controls, the frequency of the TNFalpha GA heterozygote was lower in the hypertensive group, although the statistical significance was marginal (p = 0.08). This result implies an association with resistance to the disease. In addition, the frequency of the cardio-renal connective tissue weakness type was significantly higher in the hypertensive group with the TNFalpha GG genotype, as compared to the controls (p = 0.001). An association is demonstrated among TNFalpha gene polymorphism, Koreans with hypertension, and iris constitution.

  17. Association analysis of the functional monoamine oxidase A gene promotor polymorphism in migraine.

    PubMed

    Marziniak, M; Mössner, R; Benninghoff, J; Syagailo, Y V; Lesch, K-P; Sommer, C

    2004-05-01

    Migraine affects about 15% of the adult population. Serotonergic and dopaminergic systems are believed to be involved in its pathophysiology. One of the key enzymes in the degradation of serotonin and to a lesser extent of dopamine is monoamine oxidase A (MAO-A). In this study we investigated a functionally relevant gene-linked polymorphic repetitive sequence (LPR) located approximately 1.2 kb upstream of the ATG codon in the MAO-A-promotor gene. 119 patients with migraine and 229 controls were tested. The allelic distribution of the controls and the migraine patients did not show significant differences with respect to the low- and high-activity alleles. Moreover, effectiveness of the potent serotonergic antimigraine agents, triptans, which are metabolized by MAO-A, was clinically not affected by the MAO-A-LPR in our patients. These findings thus indicate that there is no association between the functional MAO-A-LPR and susceptibility to migraine.

  18. Interleukin-10 Promoter Gene Polymorphisms and Susceptibility to Tuberculosis: A Meta-Analysis

    PubMed Central

    Gao, Xuan; Chen, Junjun; Tong, Zhongkai; Yang, Guangdie; Yao, Yinan; Xu, Fei; Zhou, Jianying

    2015-01-01

    Objective As an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility. Methods We searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations. Results A total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans. Conclusions This meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection

  19. Correlation of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease: a meta-analysis.

    PubMed

    Tian, Yulong; Ge, Zhongchun; Xing, Yuliang; Sun, Yan; Ying, Jie

    2016-12-01

    Rheumatic heart disease (RHD) is a serious cardiovascular disorder worldwide. Several articles have reported the effect of angiotensin I-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in RHD risk. However, the results still remain inconsistent. The objective of the present study was to assess more precise estimations of the relationship between ACE I/D variant and RHD susceptibility. Relevant case-control studies published between January 2000 and 2016 were searched in the electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of the effect. A total of nine articles were retrieved, including 1333 RHD patients and 1212 healthy controls. Overall, our result did not detect a significant association between ACE I/D polymorphism and RHD risk under each genetic model (P > 0.05). Subgroup analysis by ethnicity showed no positive relationship in Asians as well (P > 0.05). With respect to the severity of RHD, our result found that the frequency differences between mitral valve lesion (MVL), combined valve lesion (CVL) and healthy controls were not significantly different. Furthermore, no significant association was found between female, male RHD patients and the controls regarding to the ACE I/D polymorphism. In conclusion, our result indicated that ACE I/D polymorphism might not be a risk factor for RHD progression based on the existing research results. Additional well-designed studies with larger samples are still needed to confirm these findings.

  20. Correlation of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease: a meta-analysis

    PubMed Central

    Tian, Yulong; Ge, Zhongchun; Xing, Yuliang; Sun, Yan; Ying, Jie

    2016-01-01

    Rheumatic heart disease (RHD) is a serious cardiovascular disorder worldwide. Several articles have reported the effect of angiotensin I-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in RHD risk. However, the results still remain inconsistent. The objective of the present study was to assess more precise estimations of the relationship between ACE I/D variant and RHD susceptibility. Relevant case–control studies published between January 2000 and 2016 were searched in the electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of the effect. A total of nine articles were retrieved, including 1333 RHD patients and 1212 healthy controls. Overall, our result did not detect a significant association between ACE I/D polymorphism and RHD risk under each genetic model (P > 0.05). Subgroup analysis by ethnicity showed no positive relationship in Asians as well (P > 0.05). With respect to the severity of RHD, our result found that the frequency differences between mitral valve lesion (MVL), combined valve lesion (CVL) and healthy controls were not significantly different. Furthermore, no significant association was found between female, male RHD patients and the controls regarding to the ACE I/D polymorphism. In conclusion, our result indicated that ACE I/D polymorphism might not be a risk factor for RHD progression based on the existing research results. Additional well-designed studies with larger samples are still needed to confirm these findings. PMID:27758878

  1. Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin cancer risk: a meta-analysis.

    PubMed

    Wang, Lei; Xu, Jia; Duan, Baoxue

    2017-01-01

    Non-melanoma skin cancer (NMSC) is the most common malignancy with annually rising incidence. The aim of this study was to estimate the association between three coding polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) of the DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and NMSC susceptibility. Online databases were searched to retrieve case-control studies published between January 2000 and November 2016. Pooled odds ratio (OR) and 95% confidence interval (CI) were employed to assess the strength of association. Overall, 10 relevant studies were finally included for analysis, including 3,143 NMSC patients and 3,540 controls. For each polymorphism of XRCC1 gene, there were 3,050 cases and 3,463 controls for Arg399Gln, 914 cases and 1,182 controls for Arg194Trp, and 279 cases and 413 controls for Arg280His. Our results showed that these three polymorphisms in the XRCC1 coding region were not associated with increased risk of NMSC in the total studied population. However, subgroup analysis by ethnicities demonstrated that Gln/Arg genotype of Arg399Gln polymorphism was associated with increased risk of NMSC under the heterogeneous model in Asian populations (Gln/Arg vs Arg/Arg: OR =1.39, 95% CI =1.04-1.87, P=0.03); subgroup analysis by tumor types showed that Trp/Trp genotype of Arg194Trp was positively associated with decreased cancer risk in squamous-cell skin cancer (SCC) type under the homogeneous model (Trp/Trp vs Arg/Arg: OR =0.38, 95% CI =0.16-0.92, P=0.03). Our results suggested that Arg399Gln variant of XRCC1 gene might be a risk factor for NMSC in Asian populations, and Arg194Trp variant of XRCC1 gene might be a protective factor for patients with SCC. In addition, future case-control studies are still needed to further evaluate the effect of XRCC1 polymorphisms in NMSC risk.

  2. Association between alpha-1 antichymotrypsin gene A/T polymorphism and primary intracerebral hemorrhage: a meta-analysis

    PubMed Central

    Ye, Zusen; Ye, Qiang; Shao, Bei; He, Jincai; Zhu, Zhenguo; Cheng, Jianhua; Chen, Yanyan; Chen, Siyan; Huang, Xiaoya

    2015-01-01

    The present study is to use meta-analysis to explain the association between alpha-1 antichymotrypsin (ACT) gene A/T polymorphism and the risk of primary intracerebral hemorrhage (PICH). Relevant studies before 1 June 2015 were identified by searching PubMed, Cochrane database and Science Citation Index Expanded (SCIE), and the references of retrieved articles. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to assess the strength of the association. Five independent publications, with 774 PICH cases and 940 controls, were included. There was no statistical evidence of association between ACT polymorphism and PICH risk under all genetic models in overall estimates (allele model: OR = 1.01, 95% CI = 0.80-1.28; heterozygote model: OR = 0.93, 95% CI = 0.60-1.45; homozygote model: OR = 1.03, 95% CI = 0.59-1.80; dominant model: OR = 0.97, 95% CI = 0.65-1.46; recessive model: OR = 1.06, 95% CI = 0.72-1.57). No association was found in subgroup analysis based on ethnicity, Hardy-Weinberg equilibrium, location of hematoma and blood pressure. Sensitivity analysis suggested that the combined results were stable and reliable. No significant publication bias was found by Begg’s test and Egger’s regression test. The results of our meta-analysis indicate that ACT polymorphism is unlikely to contribute to PICH susceptibility. PMID:26885003

  3. [Meta-analysis of association of tumor necrosis factor alpha and transforming growth factor beta gene polymorphisms with pneumoconiosis].

    PubMed

    Liu, Qian; Su, Wen-zhen; Shan, Yong-le; Zhang, Zhi-hu; Xu, Guang; Zhang, Wei; Zhang, Hai-dong; Wang, Rui

    2012-08-01

    To evaluate the relationship between tumor necrosis factor-alpha-238, transforming growth factor beta (509 and 869) gene polymorphisms and pneumoconiosis susceptibility. We searched published full-text from foreign language databases including Elsevier, PubMed, Wiley Online Library, EMCC, Web of Science, chinese databases containing CNKI, VIP, Wanfang, CBM and Cochrane library to collect case-control or cohort study on gene gene polymorphisms said above with pneumoconiosis susceptibility from the year January1988 to August 2011. 28 relevant articles were selected and 20 of them met the criteria. The correlated index was extracted for aggregate analysis in RevMan 4.2. Among the 20 studies, 10 articles on TNF-α238 polymorphism (including 2232 pneumoconiosis cases and 1985 control subjects), 4 articles on TGF-β509 polymorphism (including 693 pneumoconiosis cases and 663 control subjects), and 6 articles on TGF-β869 polymorphism (including 1450 pneumoconiosis cases and 1101 control subjects) were included in the current study. Meta-analysis results showed that there was a significant association between TNF-α238 polymorphism and pneumoconiosis: the population with GA and AA genotypes of TNF-α238 had higher risks to pneumoconiosis (OR = 1.53, 95%CI: 1.25 ∼ 1.88) comparing to GG genotype, and the population with A allele had higher risks to pneumoconiosis comparing to allele G (OR = 1.64, 95%CI: 1.17 ∼ 2.30). The stratified analysis showed that the people with GA and AA genotypes and A allele who were silicosis, Asian or exposed to dust had higher risks to pneumoconiosis (OR = 2.14, 95%CI: 1.20 ∼ 3.82; OR = 2.16, 95%CI: 1.20 ∼ 3.88; OR = 1.78, 95%CI: 1.01 ∼ 3.11; OR = 1.83, 95%CI: 1.04 ∼ 3.22; OR = 1.80, 95%CI: 1.21 ∼ 2.66; OR = 1.50, 95%CI: 1.23 ∼ 1.83). No significant association was found between TGF-β (509 and 869) gene polymorphisms with pneumoconiosis: In contrast to the CC genotype, the population who had CT and TT genotypes had no higher

  4. Association analysis of FABP1 gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.

    PubMed

    Chang, Hun Soo; Park, Jong Sook; Shin, Hye-Rim; Park, Byung Lae; Shin, Hyoung Doo; Park, Choon-Sik

    2014-12-01

    Previously, we used a proteomic approach to demonstrate that the protein level of fatty acid-binding protein 1 (FABP1) is increased in nasal polyps in patients with aspirin-exacerbated respiratory disease (AERD). To reveal the genetic effect of FABP1 variants, we evaluated the association of FABP1 polymorphisms with the risk of AERD in 207 asthmatics with AERD and 1019 aspirin-tolerant asthmatics (ATA). Seven polymorphisms of FABP1 were selected from the National Center for Biotechnology Information (build 36) using minor allele frequency and linkage disequilibrium criteria. The genotype and haplotype distributions were not significantly different between the AERD and ATA groups in all of the genetic models. The percent decline of forced expiratory volume in 1 second (FEV1) after the oral aspirin challenge (OAC) test did not differ according to single-nucleotide polymorphism (SNP) genotypes. In haplotype analysis, asthmatic patients who were BL2ht2 homozygotes showed a greater decline in FEV1 after the OAC test than subjects who possessed 1 or no copy of BL2ht2 (P = 0.035). However, these observations were not significant after correction for multiple comparisons (corrected P value = 1.00). Neither genotype nor haplotype was associated with the presence of nasal polyposis in the study subjects. Although we did not find a significant association between the FABP1 polymorphisms and AERD, our data suggest that the 7 SNPs are not associated with the increased expression of FABP1 in asthmatic patients with AERD. Further studies of epigenetic factors that may contribute to the increased expression of FABP1 in AERD should be performed.

  5. Analysis of the genetic effects of prolactin gene polymorphisms on chicken egg production.

    PubMed

    Li, Hui-Fang; Shu, Jing-Ting; Du, Yu-Feng; Shan, Yan-Ju; Chen, Kuan-Wei; Zhang, Xue-Yu; Han, Wei; Xu, Wen-Juan

    2013-01-01

    Chicken prolactin (PRL) is a physiological candidate gene for egg production. Variations of T8052C and G8113C in exon 5 of PRL gene may associate with chicken egg production. The objective of the study was to investigate the association of these two single nucleotide polymorphisms in PRL gene with egg production of Recessive White chickens and Qingyuan Partridge chickens. Genotyping was performed by polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The T8052C and G8113C of PRL were significantly associated with age at first egg (AFE) and total egg number at 300 days of age (EN 300). A significant association was also found between T8052C-G8113C haplotypes and AFE as well as EN300, the H2H3 was the most advantageous diplotype for egg production. We putatively drew the conclusion that these two SNPs in PRL gene as well as their haplotypes could be used as the potential molecular markers for egg production traits in chicken.

  6. Analysis of the association of non-synonymous polymorphisms in ADH genes with hazardous drinking in HIV-1 positive individuals.

    PubMed

    Wolf, Jonas Michel; Simon, Daniel; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Lunge, Vagner Ricardo

    2017-08-23

    Hazardous drinking (HD) is a serious health problem in people infected with human immunodeficiency virus type 1 (HIV-1). Single nucleotide polymorphisms (SNPs) in alcohol dehydrogenase (ADH) genes have been associated with HD in different populations, but there was no data about this in HIV-1 positive individuals. This study investigated the association of four non-synonymous SNPs in ADH genes (Arg48His and Arg370Cys in ADH1B gene; Arg272Gln and Ile350Val in ADH1C gene) with HD in people living with HIV-1. This case-control study included 365 HIV-1 positive individuals (121 with HD and 244 without HD). Socio-demographic variables were collected with a standardized individual questionnaire. HD (score ≥8) and binge drinking (BD) (drinks on the same occasion ≥5) were detected with the Alcohol Use Disorders Identification Test (AUDIT). The four SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. The Bonferroni correction was used (considering the four SNPs studied). There were not significant differences in the frequencies of Arg370Cys, Arg272Gln, and Ile350Val polymorphisms between HD cases and controls. Otherwise, Arg/His genotype (rs1229984) in ADH1B gene showed a protective effect against HD (aOR = 0.36; 95% CI: 0.14-0.90) and BD (aOR = 0.49; 95% CI: 0.21-0.95). Nevertheless, these differences were no longer significant after Bonferroni correction. The results of this study suggest a possible effect of the Arg48His genotype on the protection against HD in HIV-1 positive individuals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Association between Genetic Polymorphisms in Interleukin Genes and Recurrent Pregnancy Loss – A Systematic Review and Meta-Analysis

    PubMed Central

    Bao, Xiao; Niu, Wenbin; Wang, Linlin; Du, Linqing; Zhang, Nan; Sun, Yingpu

    2017-01-01

    Interleukins are a group of immunomodulatory proteins that mediate a variety of immune reactions in the human body. To investigate the association between interleukin gene polymorphisms and recurrent pregnancy loss (RPL), we reviewed 21 studies from MEDLINE, EMBASE, OVID SP and PubMed to evaluate RPL-related interleukin gene polymorphisms. Meta-analysis was performed on 12 of the polymorphisms, and a review included the others. Our integrated results indicated that IL-1β (-511C/T) (P = 0.02, 95% CI 0.77[0.62,0.96]), IL-6 (-634C/G) (P<0.001, 95% CI 2.91[2.01,4.22]), IL-10 (-1082G/A, –819T/C) (P = 0.01, 95% CI 0.80[0.67,0.96]; P<0.01, 95% CI 0.66[0.49,0.89]), and IL-18 (-137G/C, -105G/A) (P<0.01, 95% CI 1.69[1.24,2.31]; P = <0.01, 95% CI 1.41[1.17,1.70]) consistently associated with RPL after meta-analysis. IL-17A rs2275913 and IL-17F rs763780, IL-21 rs2055979 and rs13143866, IL-1β (-31C/T), IL-6 (-2954G/C), and IL-10 (-536A/G) were reported only once as having a significant association with RPL. The potential mechanism underlying miscarriage and these polymorphisms and future research directions are also discussed. PMID:28103273

  8. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy

    PubMed Central

    Luo, Shasha; Wang, Furu; Shi, Chao; Wu, Zhifeng

    2016-01-01

    Aims: To shed light on the conflicting findings of the association between the methylenetetrahydrofolate reductase gene (MTHFR) 677C/T polymorphism and the risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods: A predefined search was performed on 1747 DR cases and 3146 controls from 18 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the sizes of overall and stratification effects of the MTHFR 677C/T polymorphism on the risk of DR, as appropriate. Results: Risks were evaluated by odds ratios (OR) with 95% confidence intervals (95% CI). We found a significant association between the MTHFR 677C/T polymorphism and the risk of DR for each genetic model (recessive model: OR = 1.67; 95% CI: 1.19–2.40 and dominant model: OR = 1.71; 95% CI: 1.28–2.28; respectively). In stratified analysis; we further found that the Asian group with both types of diabetes mellitus (DM) showed a significant association with genetic models (recessive model: OR = 2.16; 95% CI: 1.75–2.60 and dominant model: OR = 1.98; 95% CI: 1.42–2.76; respectively). Conclusions: Our study suggested that the MTHFR 677C/T polymorphism may contribute to DR development, especially in Asian populations. Prospective and additional genome-wide association studies (GWAS) are needed to clarify the real role of the MTHFR gene in determining susceptibility to DR. PMID:27517946

  9. Association between Genetic Polymorphisms in Interleukin Genes and Recurrent Pregnancy Loss - A Systematic Review and Meta-Analysis.

    PubMed

    Zhang, Meixiang; Xu, Jiawei; Bao, Xiao; Niu, Wenbin; Wang, Linlin; Du, Linqing; Zhang, Nan; Sun, Yingpu

    2017-01-01

    Interleukins are a group of immunomodulatory proteins that mediate a variety of immune reactions in the human body. To investigate the association between interleukin gene polymorphisms and recurrent pregnancy loss (RPL), we reviewed 21 studies from MEDLINE, EMBASE, OVID SP and PubMed to evaluate RPL-related interleukin gene polymorphisms. Meta-analysis was performed on 12 of the polymorphisms, and a review included the others. Our integrated results indicated that IL-1β (-511C/T) (P = 0.02, 95% CI 0.77[0.62,0.96]), IL-6 (-634C/G) (P<0.001, 95% CI 2.91[2.01,4.22]), IL-10 (-1082G/A, -819T/C) (P = 0.01, 95% CI 0.80[0.67,0.96]; P<0.01, 95% CI 0.66[0.49,0.89]), and IL-18 (-137G/C, -105G/A) (P<0.01, 95% CI 1.69[1.24,2.31]; P = <0.01, 95% CI 1.41[1.17,1.70]) consistently associated with RPL after meta-analysis. IL-17A rs2275913 and IL-17F rs763780, IL-21 rs2055979 and rs13143866, IL-1β (-31C/T), IL-6 (-2954G/C), and IL-10 (-536A/G) were reported only once as having a significant association with RPL. The potential mechanism underlying miscarriage and these polymorphisms and future research directions are also discussed.

  10. Polymorphism analysis in estrogen receptors alpha and beta genes and their association with infertile population in Pakistan

    PubMed Central

    Liaqat, Sinha; Hasnain, Shahida; Muzammil, Saima; Hayat, Sumreen

    2015-01-01

    Studies on polymorphism of estrogen receptor (ESR) alpha and beta genes have been mostly implicated in infertility, but the results have been controversial due to lack of comprehensive data. The present study focused on association of ESR genes with both male and female infertility. In ESRα, PvuII (rs2234693) and XbaI (rs9340799) were studied while in ESRβ gene, risk of infertility was determined for silent G/A RsaI (rs1256049) polymorphism. Total 124 subjects (74 cases and 50 controls) were part of this study having primary infertility. Restriction fragment length polymorphism (RFLP) was performed with PvuII, XbaI and RsaI to determine polymorphism. Correlation between age and follicle stimulating hormone (FSH) of cases and controls was determined and no association was found between infertility and FSH hormone. Heterozygous AG genotype of XbaI polymorphism (P= 2.505e-06) and heterozygous TC genotype (P= 0.00003) in PvuII polymorphism were strongly associated with risk of infertility. In ESRβ gene, there was lack of polymorphism for RsaI in our population as all subjects were homozygous (GG). Haplotype frequencies showed that XbaI and PvuII polymorphisms are in strong linkage disequilibrium. This study shows that in our population XbaI and PvuII polymorphisms of ESRα are associated with risk of infertility. PMID:27065769

  11. [Analysis on single nucleotide polymorphisms of porcine myostatin gene in different breeds].

    PubMed

    Jiang, Y L; Li, N; Wu, C X; Du, L X

    2001-01-01

    By PCR-RFLPs and PCR-SSCP approach, three single nucleotide polymorphisms (SNPs) of porcine myostatin gene (MSTN) were analyzed in different breeds including "doubled-muscled" Yorkshire, Yorkshire, Landrace, Hamshire, Duroc, Piteran, Erhualian, Min, Hubei White and some hybrids. The three SNPs were located in the 3' encoding region, 5' promoter region and intronl region respectively. For the SNP in the 3' encoding region, which was caused by C-->T transition, the mutation frequency was relatively low: no TT genotype was detected in 274 individuals of different breeds. For the SNP in the 5' promoter region, 560 pigs were investigated. The allele T dominates in the imported lean-type pig breeds such as Yorkshire, Landrace, Duroc, Hampshire, Piteran and hybrid, however, in Erhualian and Hubei White pigs, the allele A was in majority. Polymorphism showed the similar pattern for the SNP in intron 1 region. G was the dominant allele in Yorkshire, Landrace and their hybrids, while in Erhualian and Hubei White pigs the frequency of A was much higher. Obviously they were not in Hardy-Weinberg equilibrium state. For Min and Yorshire x Erhualian pigs, they were in Hardy-Weinberg equilibrium state for the SNPs in the 5' promoter region and (or) intron 1 region. The frequency for the A alleles of SNPs in the 5' promoter region and intron 1 region was higher for "double-muscled" Yorkshire than for Yorkshire and linkage for these two mutation sites was also observed.

  12. Rapid Identification of Rhizobia by Restriction Fragment Length Polymorphism Analysis of PCR-Amplified 16S rRNA Genes

    PubMed Central

    Laguerre, Gisèle; Allard, Marie-Reine; Revoy, Françoise; Amarger, Noelle

    1994-01-01

    Forty-eight strains representing the eight recognized Rhizobium species, two new Phaseolus bean Rhizobium genomic species, Bradyrhizobium spp., Agrobacterium spp., and unclassified rhizobia from various host plants were examined by restriction fragment length polymorphism (RFLP) analysis of 16S rRNA genes amplified by polymerase chain reaction (PCR). Twenty-one composite genotypes were obtained from the combined data of the RFLP analysis with nine endonucleases. Species assignments were in full agreement with the established taxonomic classification. Estimation from these data of genetic relationships between and within genera and species correlated well with previously published data based on DNA-rRNA hybridizations and sequence analysis of 16S rRNA genes. This PCR-RFLP method provides a rapid tool for the identification of root nodule isolates and the detection of new taxa. Images PMID:16349165

  13. Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis.

    PubMed

    Katsarou, Martha-Spyridoula; Latsi, Rosana; Papasavva, Maria; Demertzis, Nikolaos; Kalogridis, Thodoris; Tsatsakis, Aristides M; Spandidos, Demetrios A; Drakoulis, Nikolaos

    2016-07-01

    Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by increased dietary iron absorption. Due to the absence of an effective excretory mechanism, the excess iron in the body may accumulate resulting in toxic effects. The HFE gene also affects the activity of hepcidin, a hormone which acts as a negative regulator of iron metabolism. In this study, we performed a population-based analysis of the distribution of three hemochromatosis-related polymorphisms in the HFE gene (rs1800562, rs1799945 and rs1800730). DNA from 1,446 non‑related individuals of Greek ethnicity was collected and analyzed, either from whole blood or buccal swabs. The frequency distribution of these HFE gene polymorphisms was then determined. The results revealed that in our Greek population cohort (gr) the frequencies of each polymorphism were as follows: rs1800562: GG (wild‑type)=97.0%, GA=1.5%, AA=1.5%; rs1799945: CC (wild‑type)=74.4%, CG=23.4%, GG=2.2%; rs1800730: AA (wild‑type)=98.1%, AT=1.5% and TT=0.4%. No association between the HFE polymorphisms rs1800562, rs1799945 and rs1800730 and gender could be established. As regards the rs1800562 polymorphism, the A allele (mutant) was ~1.8‑fold more frequent in the European population (eur) than in the Greek population [(gr)=2,3%<(eur)=4%]. As for the rs1799945 polymorphism, the G allele (mutant) was 1.2‑fold more frequent in the European population than in the Greek population [(gr)=13,9%<(eur)=17%]. As regards the rs1800730 polymorphism, the T allele (mutant) was ~1.7‑fold more frequent in the European population than in the Greek population [(gr)=1.2%<(eur)=2%]. However, these pathogenic mutations were found more frequently in the Greek population compared to the global population (gl) [rs1800562: (gl)=1%<(gr)=2,3%; rs1799945: (gl)=7%<(gr)=13,9%; rs1800730: (gl)=<1%<(gr)=1.2%]. This suggests that the Greek population may differ genetically from the northern European population

  14. Analysis of transforming growth factor ß1 gene polymorphisms in patients with systemic sclerosis

    PubMed Central

    Crilly, A; Hamilton, J; Clark, C; Jardine, A; Madhok, R

    2002-01-01

    Objectives: To determine the distribution of transforming growth factor ß1 (TGFß1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated. Methods: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFß1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing. Results: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, χ2=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, χ2=5, 1df, p=0.02 and controls v lSSc, χ2=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, χ2=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, χ2=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon. Conclusions: These results suggest that patients with SSc are genetically predisposed to high TGFß1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc. PMID:12117671

  15. Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes.

    PubMed

    Tavira, Beatriz; Coto, Eliecer; Garciá, Eliecer Coto; Díaz-Corte, Carmen; Ortega, Francisco; Arias, Manuel; Torres, Armando; Díaz, Juan M; Selgas, Rafael; López-Larrea, Carlos; Campistol, Josep M; Alvarez, Victoria; Alvarezca, Victoria

    2011-05-01

    Tacrolimus (Tac) is an immunosuppressive drug used to prevent post-transplant (PT) organ rejection. Continuous Tac monitoring is necessary to adjust the dose and prevent toxicity or rejection. Tac is metabolized by cytochrome-P450 (CYP) enzymes, and variation at the CYP and other drug metabolizing enzymes could influence Tac bio-availability and dose requirements. Our aim was to define the effect of DNA variants at 16 drug metabolising enzymes on Tac dose in patients with kidney transplants. The REDINREN Pharmacogenetics Project was a multicenter study designed to evaluate the effect of DNA polymorphisms on Tac dose requirements. A total of 200 patients who received a first cadaveric kidney and Tac as primary immunosuppressive drug were genotyped for 96 DNA polymorphisms on 16 genes. Significant associations were further replicated in a second group of 200 patients. The Tac daily dose was adjusted to achieve a blood concentration of 10-15 ng/mL in the period 0-3 months PT, and 5-10 ng/mL thereafter. The dose of tacrolimus dose and blood concentrations were compared between genotypes at 1 week, 6 months, and 1 year PT. The CYP3A5 genotype (SNP rs776746) was the strongest predictor of Tac dose requirements. Patients who were CYP3A5*3*3 (CYP3A5 non-expressors) received significantly higher Tac dose at 1 week, 6 months, and 1 year PT (p<0.0001). At 1 week, 41% of the CYP3A5 non-expressors achieved target blood concentrations compared to 26% of the CYP3A5 expressors (p=0.007). We also found a significant effect of CYP3A4 genotype (SNP rs2740574) on Tac dose requirements in patients who were CYP3A5 non-expressors. None of the other polymorphisms were related to Tac dose requirements or modified the effect of the CYP3A5 genotype. rs776746 (CYP3A5) and rs2740574 (CYP3A4) were the only SNPs associated with Tac dosage. The genotyping of these polymorphisms could be a useful pharmacogenetic tool to determine the Tac dose immediately after transplantation.

  16. Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

    PubMed

    Deng, Yang; Wang, Jue; Wang, Ling; Du, Yan

    2017-02-28

    Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15(th) 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

  17. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review.

    PubMed

    Rai, Himanshu; Parveen, Farah; Kumar, Sudeep; Kapoor, Aditya; Sinha, Nakul

    2014-01-01

    Several association studies of endothelial nitric oxide synthase (NOS3) gene polymorphisms with respect to coronary artery disease (CAD) have been published in the past two decades. However, their association with the disease, especially among different ethnic subgroups, still remains controversial. This prompted us to conduct a systematic review and an updated structured meta-analysis, which is the largest so far (89 articles, 132 separate studies, and a sample size of 69,235), examining association of three polymorphic forms of the NOS3 gene (i.e. Glu298Asp, T786-C and 27 bp VNTR b/a) with CAD. In a subgroup analysis, we tested their association separately among published studies originating predominantly from European, Middle Eastern, Asian, Asian-Indian and African ancestries. The pooled analysis confirmed the association of all the three selected SNP with CAD in three different genetic models transcending all ancestries worldwide. The Glu298Asp polymorphism showed strongest association (OR range = 1.28-1.52, and P<0.00001 for all comparisons), followed by T786-C (OR range = 1.34-1.42, and P<0.00001 for all comparisons) and 4b/a, (OR range = 1.19-1.41, and P ≤ 0.002 for all comparisons) in our pooled analysis. Subgroup analysis revealed that Glu298Asp (OR range = 1.54-1.87, and P<0.004 for all comparisons) and 4b/a (OR range = 1.71-3.02, and P<0.00001 for all comparisons) have highest degree of association amongst the Middle Easterners. On the other hand, T786-C and its minor allele seem to carry a highest risk for CAD among subjects of Asian ancestry (OR range = 1.61-1.90, and P ≤ 0.01 for all comparisons).

  18. Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts

    PubMed Central

    2013-01-01

    Introduction Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk. Methods We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). Results In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2

  19. Lack of association between endothelial nitric oxide synthase gene polymorphisms with vasculitis: a meta-analysis.

    PubMed

    Cheng, Y; Xiong, M; Liu, Y; Tang, B

    2015-01-01

    We carried out this meta-analysis to evaluate the relationship between eNOS polymorphisms (G894T, T-786C, and intron-4ba) and vasculitis. We systematically searched PubMed, EMBASE and the Cochrane Library for related genetic association studies. The associations between the G894T, T-786C and intron 4ba polymorphisms of eNOS and vasculitis were conducted using the recessive model and the dominant model. Odds ratio (OR) with 95% confidence interval (CI) of each study were calculated. Cochran's Q test was used to evaluate the between-study heterogeneity. A total of 17 studies were included in our study. Twelve studies with 1213 cases and 1499 controls were included in the G894T association study. The pooled OR of T allele compared to C allele in recessive model was 1.19 (95%CI: 0.76-1.87, p=0.44) in dominant model and was 1.25 (95%CI: 0.70-2.23, p=0.56) in recessive model, respectively. Nine studies with 910 cases and 1062 controls were included in the intron -4ba association study. The pooled OR of b allele compared with intron-4a allele was 1.02 (95%CI: 0.60-1.72, p=0.95) in dominant model and was 0.84 (95%CI: 0.58-1.21, p=0.35) in recessive model. No association was found between T-786C and vasculitis in both the dominant 0.81(95% CI: 0.59-1.11, p=0.19) and recessive model 0.87 (95%CI: 0.55-1.36, p=0.53). The eNOS G894T, T-786C and intron4ba polymorphisms are not associated with vasculitis.

  20. Vitamin D Receptor Gene, Matrix Metalloproteinase 3 Polymorphisms and the Risk of Intervertebral Disc Degeneration Susceptibility: Meta-Analysis

    PubMed Central

    Huang, Yongjing; Zhao, Shujie; Xu, Nanwei

    2016-01-01

    Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76–1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59–1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70–1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45–1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22–1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53–0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77–4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75–6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72–3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility. PMID:27790329

  1. The -765G>C polymorphism in the cyclooxygenase-2 gene and digestive system cancer: a meta-analysis.

    PubMed

    Zhao, Fen; Cao, Yue; Zhu, Hong; Huang, Min; Yi, Cheng; Huang, Ying

    2014-01-01

    Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.

  2. Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

    PubMed

    Barbosa, A M; Silva, K S F; Lagares, M H; Rodrigues, D A; da Costa, I R; Morais, M P; Martins, J V M; Mascarenhas, R S; Campedelli, F L; Moura, K K V O

    2017-09-21

    The coronary arteriosclerotic disease is the most common cardiovascular disease. Atherosclerosis affects large- and medium-sized arteries leading to severe thrombosis or artery stenosis that could evolve to myocardial infarction, ischemic stroke, ischemic injury of kidneys and intestines, and several other life-threatening clinical manifestations. Nitric oxide has been shown to be a promising therapeutic agent against cardiovascular diseases. The eNOS gene assumes several important functions, including regulation of vascular tone and regional blood flow, the suppression of vascular smooth muscle cell proliferation, and modulation of leukocyte-endothelium interactions. The T786C polymorphism is an important point mutation, where thymine is changed to cytosine. T786C significantly reduces the activity of the eNOS promoter gene. Two hundred and ninety-seven peripheral blood samples were collected from patients with the previous diagnosis of atherosclerotic disease based on clinical examination and confirmed by imaging methods. Results were compared using the chi-square test and the G-test. In the present study, the TC genotype was more frequent in both case and control groups with no statistically significant difference. Comparing the relation TC/TT and CC genotypes in the case and control groups, there was no statistically significant difference. No significant difference was found when genotypes were analyzed regarding gender and smoking. Our results suggest a strong tendency of the T allele, in single or double dose, to be associated with atherosclerosis that was not confirmed by the scientific data.

  3. The association of TNF-308 (G/A) gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis

    PubMed Central

    Sun, Qing; Guo, Xuedan; Wang, Qi; Zhao, Fan

    2016-01-01

    Objective Many studies have examined the association between the TNF-308 G/A polymorphism gene polymorphisms and hepatocellular carcinoma risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Methods The PubMed and CNKI (China National Knowledge Infrastructure) database was searched for case-control studies. Odds ratios (OR) with 95% CIs were used to determine the strength of association between the TNF-308 G/A polymorphisms and HCC risk. The pooled ORs for the risk associated with the TNF-308 G/A genotype, the A carriers (A/G + A/A) vs. the wild-type homozygotes (G/G), A/A vs. G/G were calculated, respectively. Subgroup analyses were done by ethnicity and smoking status. Heterogeneity assumptions were assessed by chi-square-based Q-test. Results Ultimately, 21 studies, comprising 2,923 hepatocellular carcinoma cases and 4,323 controls were included. Overall, the A carriers (G/A + A/A) vs. the wild-type homozygotes (G/G), the pooled OR was 1.05 (95% CI, 0.93-1.19; P=0.000 for heterogeneity), for A/A vs. G/G the pooled OR was 1.07 (95% CI, 0.95-1.21; P=0.007 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among non-Asians. However, for Asians, significantly risks were not found. Conclusions The TNF-308 G/A polymorphisms are not associated with hepatocellular carcinoma risk among Asians, but for non-Asians. PMID:27877013

  4. Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

    PubMed

    Wu, Shuai; Han, Yan; Hu, Qiang; Zhang, Xiaojie; Cui, Guangcheng; Li, Zezhi; Guan, Yangtai

    2017-05-01

    Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P < 0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

  5. Analysis of polymorphisms and selective pressures on ama1 gene in Plasmodium knowlesi isolates from Sabah, Malaysia.

    PubMed

    Chua, Chuen Yang; Lee, Ping Chin; Lau, Tiek Ying

    2017-09-01

    The apical membrane antigen-1 (AMA-1) of Plasmodium spp. is a merozoite surface antigen that is essential for the recognition and invasion of erythrocytes. Polymorphisms occurring in this surface antigen will cause major obstacles in developing effective malaria vaccines based on AMA-1. The objective of this study was to characterize ama1 gene in Plasmodium knowlesi isolates from Sabah. DNA was extracted from blood samples collected from Keningau, Kota Kinabalu and Kudat. The Pkama1 gene was amplified using nested PCR and subjected to bidirectional sequencing. Analysis of DNA sequence revealed that most of the nucleotide polymorphisms were synonymous and concentrated in domain I of PkAMA-1. Forteen haplotypes were identified based on amino acid variations and haplotype K5 was the most common haplotype. dN/dS ratios implied that purifying selection was prevalent in Pkama1 gene. Fu and Li's D and F values further provided evidence of negative selection acting on domain II of Pkama1. Lownucleotide diversitywas also detected for the Pkama1 sequences,which is similar to reports on Pkama1 from Peninsular Malaysia and Sarawak. The presence of purifying selection and low nucleotide diversity indicated that domain II of Pkama1 can be used as a target for vaccine development.

  6. Wnt antagonist gene polymorphisms and renal cancer

    PubMed Central

    Hirata, Hiroshi; Hinoda, Yuji; Nakajima, Koichi; Kikuno, Nobuyuki; Yamamura, Soichiro; Kawakami, Kazumori; Suehiro, Yutaka; Tabatabai, Z. Laura; Ishii, Nobuhisa; Dahiya, Rajvir

    2014-01-01

    Purpose Epigenetic silencing of several Wnt pathway related genes has been reported in renal cancer. Except for the TCF4 gene, there are no reports regarding Wnt pathway gene polymorphisms in renal cancer. Therefore, we hypothesized that the polymorphisms in Wnt signaling genes may be risk factors for renal cancer. Experimental Design A total of 210 patients (145 male and 65 female) with pathologically confirmed renal cell carcinoma (RCC), and 200 age- and sex-matched control individuals were enrolled in this study. We genotyped 14 SNPs in six genes including DKK2 (rs17037102, rs419558, rs447372), DKK3 (rs3206824, rs11022095, rs1472189, rs7396187, rs2291599), DKK4 (rs2073664), sFRP4 (rs1802073, rs1802074), SMAD7 (rs12953717), DAAM2 (rs6937133, rs2504106) using PCR-RFLP and direct sequencing in RCC and age-matched healthy subjects. We also tested the relationship between these polymorphisms and clinicopathologic data including gender, grade, tumor stage, lymph-node involvement, distant metastasis, and overall survival. Results A significant decrease in the frequency of the G/A+A/A genotypes in the DKK3 codon335 rs3206824 was observed in RCC patients compared with controls. The frequency of the rs3206824 (G/A) A- rs7396187 (G/C) C haplotype was significantly lower in RCC compared with other haplotypes. We also found that DKK3 rs1472189 C/T is associated with distant metastasis and furthermore, DKK2 rs17037102 G homozygous patients had a decreased risk for death by multivariate Cox regression analysis. Conclusions This is the first report documenting that DKK3 polymorphisms are associated with RCC and that the DKK2 rs17037102 polymorphism may be a predictor for survival in RCC patients after radical nephrectomy. PMID:19562778

  7. Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular events: four studies and a meta-analysis.

    PubMed

    DE Gaetano, M; Quacquaruccio, G; Pezzini, A; Latella, M C; DI Castelnuovo, A; Del Zotto, E; Padovani, A; Lichy, C; Grond-Ginsbach, C; Gattone, M; Giannuzzi, P; Nowak, M; Novak, N; Dorn, J; Trevisan, M; Donati, M B; Iacoviello, L

    2009-09-01

    The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92). TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

  8. Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites.

    PubMed

    Wang, Shuang; Huang, Song; Liu, Nianjun; Chen, Liang; Oh, Cheongeun; Zhao, Hongyu

    2005-12-30

    There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput genotyping technologies. In this study, we compared the performance of whole-genome scans using SNPs with microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were used in our analyses. We found that the results from the two scans had good overall concordance. One region on chromosome 2 and two regions on chromosome 7 showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both the SNP and microsatellite scans. The different results observed between the two scans may be explained by the difference observed in information content between the SNPs and the microsatellites.

  9. Gene polymorphisms, apoptotic capacity and cancer risk.

    PubMed

    Imyanitov, Evgeny N

    2009-04-01

    Programmed cell death has been implicated in various aspects of cancer development. Apoptotic capacity is a subject of significant interindividual variations, which are largely attributed to hereditary traits. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk in various ways. Low activity of apoptosis may favor cancer development because of the failure to eliminate cellular clones carrying DNA damage and propensity to inflammation, but may also protect against malignancy due to preservation of antitumor immune cells. Phenotyping studies assessing cell death rate in cancer patients versus healthy controls are limited in number and produced controversial results. TP53 R72P polymorphism is the only SNP whose functional impact on apoptotic response has been replicated in independent investigations. Intriguingly, meta-analysis of TP53 genotyping studies has provided evidence for the association between apoptosis-deficient TP53 genotype and tumor susceptibility. Systematic analysis of cancer-predisposing relevance of other apoptotic gene SNPs remains to be done.

  10. Polymorphism T→C of gene CYP17 promoter and polycystic ovary syndrome risk: a meta-analysis.

    PubMed

    Li, Ya; Liu, Fei; Luo, Shan; Hu, Han; Li, Xiao-Hong; Li, Shang-Wei

    2012-03-01

    The T→C polymorphism of CYP17 gene has been inconsistently associated with polycystic ovary syndrome (PCOS) risk. We examined the association by performing a meta-analysis. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP17 polymorphism and PCOS were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (CC vs. TT, TC vs. TT), dominant model (CC+TC vs. TT), and recessive model (CC vs. TC+TT). Subgroup analyses were performed by ethnicity, country, Hardy-Weinberg equilibrium (HWE) in controls and study sample size. This meta-analysis included 10 case-control studies, which included 1321 PCOS cases and 1017 controls. Overall, the variant genotypes (CC and TC) were not associated with PCOS risk, compared with the wild-type TT homozygote. Similarly, no associations were found in the dominant and recessive models. Stratified analyses by ethnicity/country also detected no significant association. However, limiting the analysis to the studies within HWE, a significantly increased risk was observed (TC vs. TT, OR=1.44, 95% CI=1.10-1.88; dominant model, OR=1.41, 95% CI=1.10-1.81). Moreover, when stratifying by study sample size, a significantly elevated risk was found among small sample studies (≤200 subjects), but not among large sample studies (> 200 subjects). This meta-analysis suggests that the CYP17 T/C polymorphism may be not associated with PCOS risk, while the observed increase in risk of PCOS may be due to small-study bias. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Analysis of Horse Myostatin Gene and Identification of Single Nucleotide Polymorphisms in Breeds of Different Morphological Types

    PubMed Central

    Dall'Olio, Stefania; Fontanesi, Luca; Nanni Costa, Leonardo; Tassinari, Marco; Minieri, Laura; Falaschini, Adalberto

    2010-01-01

    Myostatin (MSTN) is a negative modulator of muscle mass. We characterized the horse (Equus caballus) MSTN gene and identified and analysed single nucleotide polymorphisms (SNPs) in breeds of different morphological types. Sequencing of coding, untranslated, intronic, and regulatory regions of MSTN gene in 12 horses from 10 breeds revealed seven SNPs: two in the promoter, four in intron 1, and one in intron 2. The SNPs of the promoter (GQ183900:g.26T>C and GQ183900:g.156T>C, the latter located within a conserved TATA-box like motif) were screened in 396 horses from 16 breeds. The g.26C and the g.156C alleles presented higher frequency in heavy (brachymorphic type) than in light breeds (dolichomorphic type such as Italian Trotter breed). The significant difference of allele frequencies for the SNPs at the promoter and analysis of molecular variance (AMOVA) on haplotypes indicates that these polymorphisms could be associated with variability of morphology traits in horse breeds. PMID:20706663

  12. Analysis of horse myostatin gene and identification of single nucleotide polymorphisms in breeds of different morphological types.

    PubMed

    Dall'Olio, Stefania; Fontanesi, Luca; Nanni Costa, Leonardo; Tassinari, Marco; Minieri, Laura; Falaschini, Adalberto

    2010-01-01

    Myostatin (MSTN) is a negative modulator of muscle mass. We characterized the horse (Equus caballus) MSTN gene and identified and analysed single nucleotide polymorphisms (SNPs) in breeds of different morphological types. Sequencing of coding, untranslated, intronic, and regulatory regions of MSTN gene in 12 horses from 10 breeds revealed seven SNPs: two in the promoter, four in intron 1, and one in intron 2. The SNPs of the promoter (GQ183900:g.26T>C and GQ183900:g.156T>C, the latter located within a conserved TATA-box like motif) were screened in 396 horses from 16 breeds. The g.26C and the g.156C alleles presented higher frequency in heavy (brachymorphic type) than in light breeds (dolichomorphic type such as Italian Trotter breed). The significant difference of allele frequencies for the SNPs at the promoter and analysis of molecular variance (AMOVA) on haplotypes indicates that these polymorphisms could be associated with variability of morphology traits in horse breeds.

  13. Association analysis of polymorphic CGG repeat in 5' UTR of the reelin and VLDLR genes with schizophrenia.

    PubMed

    Akahane, Akihisa; Kunugi, Hiroshi; Tanaka, Hiroshi; Nanko, Shinichiro

    2002-11-01

    Several lines of evidence suggest a possible role for reelin in the pathogenesis of neurodevelopmental diseases, particularly schizophrenia. Genes encoding reelin and proteins involved in the signal pathway of reelin are thus candidate genes for schizophrenia. We examined the polymorphic CGG repeat in the 5'-untranslated region (UTR) of the reelin gene, which was recently found to be associated with autistic disorder, and the CGG repeat in the 5' UTR region of the very low density protein receptor (VLDLR) gene, which was reported to be associated with sporadic Alzheimer's disease, for allelic association with schizophrenia. The subjects consisted of 150 patients and 150 controls matched for sex, age and ethnicity (Japanese). We found no significant association of schizophrenia with the trinucleotide repeat polymorphism of the reelin or VLDLR genes, suggesting that these polymorphisms do not have a major role in the pathogenesis of the disease. Copyright 2002 Elsevier Science B.V.

  14. Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis

    PubMed Central

    Yi, Yong-Xiang; Han, Jian-Bo; Zhao, Liang; Fang, Yuan; Zhang, Yu-Feng; Zhou, Guang-Yao

    2015-01-01

    This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-α gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-α -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-α -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-α -238G>A, while TNF-α -308G>A is in African population. PMID:26884992

  15. The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis.

    PubMed

    Au, Anthony; Griffiths, Lyn R; Cheng, Kian-Kai; Wee Kooi, Cheah; Irene, Looi; Keat Wei, Loo

    2015-12-15

    Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11-1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02-1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.

  16. The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis

    PubMed Central

    Au, Anthony; Griffiths, Lyn R.; Cheng, Kian-Kai; Wee Kooi, Cheah; Irene, Looi; Keat Wei, Loo

    2015-01-01

    Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11–1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02–1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01–1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke. PMID:26666837

  17. Rapid detection of functional gene polymorphisms of TLRs and IL-17 using high resolution melting analysis

    PubMed Central

    Teräsjärvi, Johanna; Hakanen, Antti; Korppi, Matti; Nuolivirta, Kirsi; Gröndahl-Yli-Hannuksela, Kirsi; Mertsola, Jussi; Peltola, Ville; He, Qiushui

    2017-01-01

    Genetic variations in toll-like receptors (TLRs) and IL-17A have been widely connected to different diseases. Associations between susceptibility and resistance to different infections and single nucleotide polymorphisms (SNPs) in TLR1 to TLR4 and IL17A have been found. In this study, we aimed to develop a rapid and high throughput method to detect functional SNPs of above mentioned proteins. The following most studied and clinically important SNPs: TLR1 (rs5743618), TLR2 (rs5743708), TLR3 (rs3775291), TLR4 (rs4986790) and IL17 (rs2275913) were tested. High resolution melting analysis (HRMA) based on real-time PCR combined with melting analysis of a saturating double stranded-DNA binding dye was developed and used. The obtained results were compared to the “standard” sequencing method. A total of 113 DNA samples with known genotypes were included. The HRMA method correctly identified all genotypes of these five SNPs. Co-efficient values of variation of intra- and inter-run precision repeatability ranged from 0.04 to 0.23%. The determined limit of qualification for testing samples was from 0.5 to 8.0 ng/μl. The identical genotyping result was obtained from the same sample with these concentrations. Compared to “standard” sequencing methods HRMA is cost-effective, rapid and simple. All the five SNPs can be analyzed separately or in combination. PMID:28148965

  18. Analysis of Association between Norepinephrine Transporter Gene Polymorphisms and Personality Traits of NEO-FFI in a Japanese Population

    PubMed Central

    Narita, Shin; Nagahori, Kenta; Numajiri, Maki; Yoshihara, Eiji; Ohtani, Nobuyo; Ishigooka, Jun

    2015-01-01

    Objective Norepinephrine is an important chemical messenger that is involved in mood and stress in humans, and is reabsorbed by the norepinephrine transporter (NET). According to Cloninger's theory, the noradrenergic system mediates the personality trait of reward dependence. Thus far, although association studies on NET gene polymorphisms and Cloninger's personality traits have been reported, they yielded inconsistent results. Therefore, in the present study we investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of the NET gene (SLC6A2) are associated with reward dependence-related traits, as assessed by the five-factor model. Methods After written informed consent was obtained from participants, the three NET gene polymorphisms were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and personality was assessed by the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) in 270 Japanese university students. Results A significant relation was found between the -3081A/T functional promoter polymorphism and NEO-FFI scores: those with the T allele exhibited a lower extraversion (E) score than those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However, there was no correlation between the other NET gene polymorphisms and E score, and no association with other dimensions and these three polymorphisms. Conclusion We conclude that the -3081A/T functional polymorphism in the NET gene may affect the extraversion of reward dependence-related traits, as measured by NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study. Further investigations are necessary using the full version of self-rating personality questionnaires. PMID:26207133

  19. Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis

    PubMed Central

    Wu, Wenlong; Zhang, Dongfeng

    2013-01-01

    Background The association between polymorphism 4b/a, T-786C and G894T in endothelial NO synthase gene (eNOS) and ischemic stroke (IS) remains controversial in Asian. A meta-analysis was performed to better clarify the association between eNOS gene and IS risk. Methods Based on the search of PubMed, Web of Science (ISI), CNKI (National Knowledge Infrastructure), Wan Fang Med Online and CBM (Chinese Biology Medical Literature Database) databases, all eligible case-control or cohort studies were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effect models were calculated. Heterogeneity among studies was evaluated using the I2. Meta-regression was used to explore the potential sources of between-study heterogeneity. Begg's test was used to estimate publication bias. Results Our study included 27 articles, contained 28 independent case–control studies, involved a total of 3,742 cases and 3,691 controls about 4b/a, 1,800 cases and 1,751 controls about T-786C and 2,747 cases and 2,872 controls about G894T. A significant association of 4a allele with increased risk of IS was found in dominant (FEM: OR = 1.498, 95% CI = 1.329–1.689), recessive (FEM: OR = 2.132, 95% CI = 1.383–3.286) and codominant (REM: OR = 1.456, 95% CI = 1.235–1.716) models. For T-786C and G894T, there were significant associations with dominant and codominant genetic models, but not with recessive genetic model. Conclusions The meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be associated with IS. PMID:23544143

  20. Endothelial NO synthase gene polymorphisms and risk of ischemic stroke in Asian population: a meta-analysis.

    PubMed

    Wang, Meiyun; Jiang, Xiubo; Wu, Wenlong; Zhang, Dongfeng

    2013-01-01

    The association between polymorphism 4b/a, T-786C and G894T in endothelial NO synthase gene (eNOS) and ischemic stroke (IS) remains controversial in Asian. A meta-analysis was performed to better clarify the association between eNOS gene and IS risk. Based on the search of PubMed, Web of Science (ISI), CNKI (National Knowledge Infrastructure), Wan Fang Med Online and CBM (Chinese Biology Medical Literature Database) databases, all eligible case-control or cohort studies were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effect models were calculated. Heterogeneity among studies was evaluated using the I(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. Begg's test was used to estimate publication bias. Our study included 27 articles, contained 28 independent case-control studies, involved a total of 3,742 cases and 3,691 controls about 4b/a, 1,800 cases and 1,751 controls about T-786C and 2,747 cases and 2,872 controls about G894T. A significant association of 4a allele with increased risk of IS was found in dominant (FEM: OR = 1.498, 95% CI = 1.329-1.689), recessive (FEM: OR = 2.132, 95% CI = 1.383-3.286) and codominant (REM: OR = 1.456, 95% CI = 1.235-1.716) models. For T-786C and G894T, there were significant associations with dominant and codominant genetic models, but not with recessive genetic model. The meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be associated with IS.

  1. A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus.

    PubMed

    Niu, Wenquan; Qi, Yue; Wu, Zhijun; Liu, Yan; Zhu, Dingliang; Jin, Wei

    2012-07-06

    Genetic association studies on the gene encoding receptor for advanced glycation end products (RAGE) and diabetes mellitus have reported conflicting results. To evaluate the association of RAGE gene four widely-evaluated polymorphisms (T-429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was conducted. A random-effects model was applied irrespective of between-study heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser, and 2843/3302 (n=13) for G1704T. Overall results detected no significant association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk. There was a trend toward an increased risk for alleles 1704T relative to 1704G (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup analysis by ethnicity indicated that allele 1704T conferred a significantly increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes mellitus indicated that association was potentiated exclusively for G1704T with diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias was observed. Our results provide convincing evidence regarding the association of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially diabetic retinopathy. Notably, this effect was more pronounced in East Asians. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Maternal gene polymorphisms involved in folate metabolism and the risk of having a Down syndrome offspring: a meta-analysis.

    PubMed

    Yang, Mei; Gong, Tian; Lin, Xiaofang; Qi, Ling; Guo, Yiyang; Cao, Zhongqiang; Shen, Min; Du, Yukai

    2013-11-01

    Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Our study aimed to arrive at a more accurate estimation. Therefore, we carried out a meta-analysis of 26, 17, 9, 15, 9 and 6 case-control studies on the relationship between maternal methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G, reduced folate carrier 1 A80G and cystathionine β-synthase 844ins68 polymorphisms and the risk of having a DS offspring. The allele contrast and model-free approach were used. Results showed marginal significant associations for MTHFR C677T, overall [odds ratio (OR) = 1.28 (1.22, 1.46) and generalised odds ratio (ORG) = 1.35 (1.16, 1.57)] and in Caucasian [OR = 1.15 (1.03, 1.29) and ORG = 1.20 (1.04, 1.38)], Asian [OR = 1.68 (1.08, 2.63) and ORG = 1.74 (1.08, 2.80)] and Brazilian [OR = 1.22 (1.04, 1.43) and ORG = 1.28 (1.06, 1.55)] populations; for MTRR A66G, overall [OR = 1.22 (1.02, 1.46) and ORG = 1.31 (1.06, 1.62)]; and for RFC1 A80G, overall [OR = 1.16 (1.02, 1.31) and ORG = 1.18 (1.01, 1.37)]. MTHFR A1298C, MTR 12756G and CBS 844ins68 polymorphisms produced non-significant results. Since potential confounders could not be ruled out completely in this meta-analysis, further studies are needed to confirm these results.

  3. OSAnalyzer: A Bioinformatics Tool for the Analysis of Gene Polymorphisms Enriched with Clinical Outcomes

    PubMed Central

    Agapito, Giuseppe; Botta, Cirino; Guzzi, Pietro Hiram; Arbitrio, Mariamena; Di Martino, Maria Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Cannataro, Mario

    2016-01-01

    Background: The identification of biomarkers for the estimation of cancer patients’ survival is a crucial problem in modern oncology. Recently, the Affymetrix DMET (Drug Metabolizing Enzymes and Transporters) microarray platform has offered the possibility to determine the ADME (absorption, distribution, metabolism, and excretion) gene variants of a patient and to correlate them with drug-dependent adverse events. Therefore, the analysis of survival distribution of patients starting from their profile obtained using DMET data may reveal important information to clinicians about possible correlations among drug response, survival rate, and gene variants. Methods: In order to provide support to this analysis we developed OSAnalyzer, a software tool able to compute the overall survival (OS) and progression-free survival (PFS) of cancer patients and evaluate their association with ADME gene variants. Results: The tool is able to perform an automatic analysis of DMET data enriched with survival events. Moreover, results are ranked according to statistical significance obtained by comparing the area under the curves that is computed by using the log-rank test, allowing a quick and easy analysis and visualization of high-throughput data. Conclusions: Finally, we present a case study to highlight the usefulness of OSAnalyzer when analyzing a large cohort of patients. PMID:27669316

  4. Polymorphism of the ADRB2 gene and response to inhaled beta- agonists in children with asthma: a meta-analysis.

    PubMed

    Finkelstein, Yaron; Bournissen, Facundo Garcia; Hutson, Janine R; Shannon, Michael

    2009-11-01

    About 9% of children have asthma, corresponding to almost 6.8 million children in the USA and 1.1 million in the UK. Asthma exacerbations are the leading cause of pediatric emergency room visits and impose a large burden on the individual, family, and society. There is mounting evidence that therapeutic failure of inhaled beta-agonists is associated with polymorphisms of the beta(2)-adrenergic receptor gene (ADRB2); specifically, mutations leading to amino acid changes at positions 16 and 27, which alter down-regulation of the beta(2)-adrenergic receptor (beta(2)AR), induce resistance to the smooth-muscle relaxing effect of beta(2)-adrenergic agonists. We conducted a meta-analysis to examine the association between ADRB2 polymorphisms and the response to inhaled beta(2)-adrenergic agonists in children with asthma. We included all published studies until November 2008, in which asthmatic children underwent testing for acute bronchodilator response, defined as > or = 15% improvement in forced expiratory volume in 1 second (FEV(1)) and single nucleotide polymorphism (SNP) genotyping for positions 16 and/or 27 of the beta(2)AR. Individual and summary odds ratios were calculated using a random effects model. We identified three case-control or family-based studies involving 960 asthmatic children (692 children with negative beta(2)-bronchodilator response, defined as < 15% improvement in FEV(1) and 268 children with positive bronchodilator response). We found a significant association between favorable therapeutic response to inhaled beta(2)-adrenergic agonists in asthmatic children and the Arg/Arg phenotype at position 16 of the beta(2)AR [OR = 1.77; 95% CI (1.01; 3.1); p = 0.029], compared with the Arg/Gly or Gly/Gly phenotypes. The beneficial effect of Arg at position 16 of the beta(2)AR was most pronounced in African-American asthmatic children [OR = 3.54; 95% CI (1.37, 9.13)]. There was no association between clinical response to beta(2)-agonists and polymorphism

  5. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms with Coronary Artery Disease: An Updated Meta-Analysis and Systematic Review

    PubMed Central

    Parveen, Farah; Kapoor, Aditya; Sinha, Nakul

    2014-01-01

    Several association studies of endothelial nitric oxide synthase (NOS3) gene polymorphisms with respect to coronary artery disease (CAD) have been published in the past two decades. However, their association with the disease, especially among different ethnic subgroups, still remains controversial. This prompted us to conduct a systematic review and an updated structured meta-analysis, which is the largest so far (89 articles, 132 separate studies, and a sample size of 69,235), examining association of three polymorphic forms of the NOS3 gene (i.e. Glu298Asp, T786-C and 27bp VNTR b/a) with CAD. In a subgroup analysis, we tested their association separately among published studies originating predominantly from European, Middle Eastern, Asian, Asian-Indian and African ancestries. The pooled analysis confirmed the association of all the three selected SNP with CAD in three different genetic models transcending all ancestries worldwide. The Glu298Asp polymorphism showed strongest association (OR range = 1.28–1.52, and P<0.00001 for all comparisons), followed by T786-C (OR range = 1.34–1.42, and P<0.00001 for all comparisons) and 4b/a, (OR range = 1.19–1.41, and P≤0.002 for all comparisons) in our pooled analysis. Subgroup analysis revealed that Glu298Asp (OR range = 1.54–1.87, and P<0.004 for all comparisons) and 4b/a (OR range = 1.71–3.02, and P<0.00001 for all comparisons) have highest degree of association amongst the Middle Easterners. On the other hand, T786-C and its minor allele seem to carry a highest risk for CAD among subjects of Asian ancestry (OR range = 1.61–1.90, and P≤0.01 for all comparisons). PMID:25409023

  6. Associations between dopamine D2 receptor gene polymorphisms and schizophrenia risk: a PRISMA compliant meta-analysis

    PubMed Central

    He, Hairong; Wu, Huanhuan; Yang, Lihong; Gao, Fan; Fan, Yajuan; Feng, Junqin; Ma, Xiancang

    2016-01-01

    Objective To determine the relationships between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia using meta-analysis. Method The PubMed, Embase, and China National Knowledge Infrastructure databases were searched to identify relevant literature published up to February 2016. The allele contrast model was used. Stata software was used for statistical analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated to evaluate the associations between dopamine D2 receptor gene polymorphisms and the risk of schizophrenia. Meta-regression and publication bias, trim-and-fill, subgroup, sensitivity, cumulative, and fail-safe number analyses were also performed. Results This meta-analysis included 81 studies. The rs1801028 and rs1799732 were associated with schizophrenia risk among Asians (P=0.04, OR =1.25, 95% CI =1.01–1.55; P<0.01, OR =0.76, 95% CI =0.63–0.92, respectively), while the rs6277 was associated with schizophrenia risk in Caucasians (P<0.01, OR=0.72, 95% CI =0.66–0.79). The rs1800497 was also associated with schizophrenia risk in population-based controls (P<0.01, OR =0.84, 95% CI =0.72–0.97). The rs6275, rs1079597, and rs1800498 were not associated with schizophrenia risk. In addition, meta-regression indicated that the controls may be sources of heterogeneity for the rs1801028 single-nucleotide polymorphism (SNP), while ethnicity may be sources of heterogeneity for the rs6277 SNP. Publication bias was significant for the rs1801028 SNP, and this result changed after the publication bias was adjusted using the trim-and-fill method. Conclusion This meta-analysis demonstrated that the rs1801028 may be a risk factor for susceptibility to schizophrenia among Asians, while the rs1799732 may be a protective factor for that population. Large-sample studies are necessary to verify the results of this meta-analysis. PMID:28003749

  7. Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis.

    PubMed

    Gu, Chongjuan; Gong, Hongxia; Zhang, Zheng; Yang, Zhao; Ma, Yongxin

    2016-07-01

    It has been reported single-nucleotide polymorphisms (SNPs) of the IL-10 promoter might be associated with the susceptibility to recurrent pregnancy loss (RPL). Owing to the inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the IL-10 promoter SNPs and RPL risk. A systematic search of studies on the association of the three SNPs with RPL was conducted in PubMed and Embase. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to pool the effect size. Eleven case-control studies on rs1800896, seven studies on rs1800871, and eight studies on rs1800872 were included. A significant association was identified between IL-10 rs1800896 with RPL risk (G versus A: OR = 1.21, 95 % CI 1.09-1.35). No evidence of association was found between rs1800871 and RPL when restricted to those studies in Hardy-Weinberg equilibrium in controls (T versus C: OR = 1.25, 95 % CI 0.76-2.06). No statistical association was demonstrated between rs1800872 and RPL (C versus A: OR = 1.08, 95 % CI 0.83-1.42). IL-10 rs1800896 significantly increases the risk of RPL, while rs1800872 is not correlated with RPL risk. No significant association is demonstrated between rs1800871 and RPL risk but this requires further investigation.

  8. No association of genetic polymorphisms in CYP1B1 with primary open-angle glaucoma: a meta- and gene-based analysis

    PubMed Central

    Dong, Shuqian; Yang, Jingyun; Yu, Weihong; Kota, Pravina; Xia, Xiaobo

    2012-01-01

    Purpose To examine the effects of genetic polymorphisms in cytochrome P450, subfamily 1, polypeptide 1 (C1P1B1) on primary open-angle glaucoma (POAG). Methods A systematic literature search was performed, and random-effects meta-analyses were used to evaluate genetic polymorphisms in CYP1B1 with POAG. A gene-based analysis was conducted to investigate the cumulative effects of genetic polymorphisms in CYP1B1. Results A total of six studies from published papers were included in our analysis. Random-effects meta-analyses failed to detect any significant association of POAG with genetic polymorphisms in CYP1B1, including rs180040, rs1056836, rs10012, rs1056827, rs1056837, and rs2567206. The gene-based analysis indicated that the cumulative effect of genetic polymorphisms in CYP1B1 is not associated with POAG (p>0.50). Conclusions We did not find any evidence of strong association of POAG with CYP1B1 genetic polymorphisms and their cumulative effect. PMID:22509109

  9. The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis

    PubMed Central

    Liu, Rui; Mo, Yuan-Yuan; Wang, Hui-Li; Tan, Yan; Wen, Xiu-Jie; Deng, Man-Jing; Yan, Hong; Li, Lei

    2016-01-01

    Accumulating evidences have demonstrated that lipopolysaccharide (LPS) represents the important etiologic factor for sepsis. Some previous studies have reported the relationship between common polymorphisms rs4986790 and rs4986791 in the coding gene for this receptor and the susceptibility to sepsis, but there were distinct divergences between those findings. We therefore designed this meta-analysis incorporated 28 published articles containing 6,537 sepsis patients and 8,832 controls for a more comprehensive conclusion on this matter. Odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to evaluate the association of toll like receptor 4 gene polymorphisms rs4986790 and rs4986791 with sepsis risk. Heterogeneity between included studies was inspected using Q test, and sensitivity analysis was implemented via sequential deletion of each included study to investigate the stability of overall estimates. Funnel plot and Egger’s test were adopted to examine publication bias across selected studies. We found no significant association for either the polymorphism rs4986790 or rs4986791 with sepsis susceptibility in total analysis under any genetic models. Neither did we after combining these two polymorphisms. The results of this meta-analysis suggest that the rs4986790 and rs4986791 polymorphisms in toll like receptor 4 gene may have no statistically significant influence on sepsis susceptibility. PMID:27958344

  10. Lack of association between the connexin 37 C1019T gene polymorphism and coronary artery disease in a Chinese population: Meta-analysis of 2,206 subjects.

    PubMed

    Li, Yan-Yan; Qian, Yun; Zhou, Chuan-Wei

    2013-05-01

    The connexin 37 (Cx37) C1019T gene polymorphism has been suggested to be correlated with increased coronary artery disease (CAD) risk, but research results remain inconsistent. To explore the relationship between the Cx37 C1019T gene polymorphism and CAD in a Chinese population, the current meta-analysis of 6 individual studies involving 1,244 CAD patients and 962 controls was conducted. The pooled odds ratios (ORs) as well as the corresponding 95% confidence intervals (CIs) were estimated using a random- or fixed-effect model. No significant association was found between Cx37 C1019T gene polymorphism and CAD in the Chinese population under the allelic (OR=0.96; 95% CI=0.59-1.56, P=0.87), recessive (OR=0.77, 95% CI=0.28-2.08, P=0.60), dominant (OR=0.990, 95% CI=0.773-1.266, P=0.934), additive (OR=1.000, 95% CI=0.736-1.359, P=1.000), homozygous (OR=1.062, 95% CI=0.598-1.887, P=0.836) or heterozygous (OR=1.017, 95% CI=0.802-1.291, P=0.888) genetic models. Cx37 C1019T gene polymorphism was not suggested to be associated with CAD susceptibility in the Chinese population. In conclusion, no association was found between Cx37 C1019T gene polymorphism and CAD in the Chinese population.

  11. [Association of cytochrome P450 2A6 gene polymorphisms with smoking behaviors:a Meta-analysis].

    PubMed

    Pan, Lulu; Li, Suyun; Zhou, Yunping; Yang, Xiaorong; Jia, Chongqi

    2015-02-01

    A Meta-analysis was performed to assess the association of defective hepatic cytochrome P450 2A6 (CYP2A6) gene with smoking behaviors. All eligible studies published up to 2014 were searched out from PubMed, China National Knowledge Internet (CNKI), ISI Web of knowledge (ISI), vip citation databases (VIP), Chinese BioMedical Literature (CBM) and Elsevier Science Direct, searching words were "smok*","nicotine dependence","CYP2A6","cytochrome P450 2A6","polymorphism","mut*"and"varia*", while 436 articles were concluded. Meta-analysis was performed using Statal 3.1. A total of ten studies were finally included. We didn't find a significant effect of defective CYP2A6 gene on smoking initiation (fixed effect model (FEM): OR = 0.90, 95%CI: 0.78-1.03, I(2) = 25.8%), smoking persistence (random effect model (REM): OR = 0.85, 95%CI: 0.59-1.23, I(2) = 66.3%) and smoking cessation (REM: OR = 0.89, 95%CI: 0.57-1.40, I(2) = 67.1%). But it showed a significant protective effect of CYP2A6*4 on smoking initiation (FEM: OR = 0.78, 95%CI: 0.61-0.99, I(2) = 28.2%), smoking persistence (FEM: OR = 0.53, 95%CI: 0.36-0.77, I(2) = 41.0%) and smoking cessation (REM: OR = 0.49, 95%CI: 0.31-0.80, I(2) = 0.0%). This Meta-analysis suggested that there was not a protective effect of defective CYP2A6 gene against smoking behaviors. But smokers with whole CYP2A6 gene deletion would be less likely to start smoking, less smoking persistence and more likely to quit smoking successful than smokers with wild CYP2A6 gene.

  12. Association analysis of vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Mexican-Mestizo women.

    PubMed

    González-Mercado, A; Sánchez-López, J Y; Regla-Nava, J A; Gámez-Nava, J I; González-López, L; Duran-Gonzalez, J; Celis, A; Perea-Díaz, F J; Salazar-Páramo, M; Ibarra, B

    2013-07-30

    We investigated associations between vitamin D receptor (VDR) gene polymorphisms, FokI T>C (rs2228570), BsmI G>A (rs1544410), ApaI G>T (rs7975232), and TaqI T>C (rs731236), with bone mineral density (BMD) in postmenopausal Mexican-Mestizo women. Three hundred and twenty postmenopausal women participated, who were classified according to World Health Organization criteria as non-osteoporotic (Non-OP; N = 88), osteopenic (Opn; N = 144), and osteoporotic (OP; N = 88). BMD measurements at the lumbar (L1-L4) spine and at the left and right femoral neck were obtained by dual-energy X-ray absorptiometry. Single nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction and TaqMan probes. Genotype and allelic frequencies of the 4 VDR SNPs were similar among the 3 groups. Polymorphic allele frequencies were as follows: FokI (C) 0.53, 0.49, 0.56; BsmI (A) 0.26, 0.22, 0.23; ApaI (T) 0.43, 0.39, 0.44; TaqI (C) 0.27, 0.22, 0.23 for the Non-OP, Opn, and OP groups, respectively. Although no associations were found between the SNPs and BMD, based on the putative function of the FokI SNP, we constructed, for the first time, the haplotype with the 4 VDR SNPs, and found that the CGGT haplotype differed between the Non- OP and OP groups (21.8 vs 31.8%, P < 0.05). The risk analysis for this haplotype was nearly significant under the dominant model (OR = 1.783, 95%CI = 0.98-3.25, P = 0.058). This result suggests a possible susceptibility effect of the C allele of the FokI SNP for the development of osteoporosis in postmenopausal Mexican-Mestizo women.

  13. Species-Specific Identification of Mycobacterium leprae by PCR-Restriction Fragment Length Polymorphism Analysis of the hsp65 Gene

    PubMed Central

    Rastogi, Nalin; Goh, Khye Seng; Berchel, Mylene

    1999-01-01

    PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene present in all mycobacteria was used in the present investigation to characterize Mycobacterium leprae. Bacilli were extracted and purified from different organs from experimentally infected armadillos and nude mice (Swiss mice of nu/nu origin). A total of 15 samples were assayed in duplicate, and the results were compared with those obtained for a total of 147 cultivable mycobacteria representing 34 species. Irrespective of its origin or viability, M. leprae strains from all the samples were uniformly characterized by two fragments of 315 and 135 bp upon BstEII digestion and two fragments of 265 and 130 bp upon HaeIII digestion. PRA is a relatively simple method and permits the conclusive identification of M. leprae to the species level. PMID:10325367

  14. Analysis of Manganese Superoxide Dismutase and Glutathione Peroxidase 1 Gene Polymorphisms in Vitiligo.

    PubMed

    Seçkin, Havva Yıldız; Kalkan, Göknur; Bütün, İlknur; Akbaş, Ali; Baş, Yalçın; Karakuş, Nevin; Benli, İsmail

    2016-08-01

    Vitiligo is a hereditary/acquired progressive pigmentation disorder characterized by discoloration of skin as a result of melanocyte dysfunction. Recent studies have proposed that oxidant/antioxidant status plays an important role in vitiligo pathogenesis because of the toxic effects on melanocytes. In this study, we aimed to investigate possible associations of MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms with vitiligo with in Turkish population. The study group consists of 57 patients with vitiligo and 69 healthy controls. Genotyping is performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms. The method used for genotyping was based on the PCR amplification and detection of polymorphisms by hybridization probes labeled with fluorescent dyes. Both the genotype and allele frequencies of MnSOD Ala-9Val (p = 0.817 and p = 0.553, respectively) and GPx1 Pro198Leu polymorphisms (p = 0.422 and p = 0.673, respectively) were not significantly different between vitiligo patients and the control group. Although no significant difference was found, this is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms in Turkish population. Further studies with large populations will be able to clarify the association better.

  15. Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.

    PubMed

    Ma, Qingtong; Qi, Can; Tie, Chong; Guo, Zhanjun

    2013-11-10

    Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.

  16. Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson's disease and multiple system atrophy in a Chinese population.

    PubMed

    Chen, YongPing; Cao, Bei; Yang, Jing; Wei, QianQian; Ou, Ru Wei; Zhao, Bi; Song, Wei; Guo, XiaoYan; Shang, HuiFang

    2015-11-01

    Whether polymorphisms rs11856808 and rs9652490 of the Leucine-rich repeat and Ig domain containing, Nogo receptor-interacting protein-1 (LINGO1) gene, as well as rs10968280, rs13362909 and rs7033345 of the LINGO2 gene, increase the risk for Parkinson's disease (PD) is controversial. Considering the overlap of the clinical and pathological characteristics among PD and multiple system atrophy (MSA), we explored the associations between these five polymorphisms and PD and MSA in a Chinese population. A total of 1055 PD patients, 320 MSA patients, and 810 healthy controls (HCs) were genotyped for these five polymorphisms in LINGO1 and LINGO 2 using Sequenom iPLEX Assay technology. Moreover, after combining our results with available published data, a meta-analysis was conducted to investigate the associations between LINGO 1 rs11856808 and rs9652490 and the risk of PD. The frequency of the minor alleles "T" of LINGO1 rs11856808 was significantly lower in PD than that in HCs (p = 0.011, OR 0.89, 95 % CI 0.81-0.97), but not in MSA. Moreover, there were no significant differences in the minor allele frequency distributions of the other four polymorphisms between PD and HCs, and between MSA and HCs. The meta-analysis showed a lack of association of rs9652490 and PD, regardless of the genetic model or ethnic origin. However, the rs11856808 allele decreased the risk of PD in patients of Asian origin in a dominant genetic model. Our findings suggest that rs11856808 plays a protective role by decreasing the risk for PD, but not for MSA, in Asian population, the other four polymorphisms do not contribute to the risk for PD and MSA.

  17. Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

    2014-03-01

    The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P < 0.00001). Genotype ApoE ɛ4/ɛ4 and ɛ4/ɛ3 have statistically significant association with AD as well (ɛ4/ɛ4: OR = 11.76, 95% CI = 6.38-21.47, P < 0.00001; ɛ4/ɛ3: OR = 3.08, 95% CI = 2.57-3.69, P < 0.00001). Furthermore, the frequency of the ApoE ɛ3 is lower in AD than that in the health controls, and the difference of ɛ3 allele is also statistically significant (OR = 0.42, 95% CI = 0.37-0.47, P < 0.00001). No significant heterogeneity was observed among all studies. This meta-analysis suggests that the subject with at least one ApoE ɛ4 allele has higher risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

  18. Single nucleotide polymorphism microarray analysis in cortisol-secreting adrenocortical adenomas identifies new candidate genes and pathways.

    PubMed

    Ronchi, Cristina L; Leich, Ellen; Sbiera, Silviu; Weismann, Dirk; Rosenwald, Andreas; Allolio, Bruno; Fassnacht, Martin

    2012-03-01

    The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (≥20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors.

  19. The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis.

    PubMed

    Liu, Yun-Sheng; Dai, Xuan; Wu, Wei; Yuan, Fang-Fen; Gu, Xue; Chen, Jian-Guo; Zhu, Ling-Qiang; Wu, Jing

    2017-04-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most highly heritable psychiatric disorders in childhood. The risk gene mutation accounts for about 60 to 90 % cases. Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the neuronal cells. A number of evidences have suggested the role of SNAP-25 in the etiology of ADHD. Notably, the animal model of coloboma mouse mutant bears a ∼2-cM deletion encompassing genes including SNAP25 and displays spontaneous hyperkinetic behavior. Previous investigators have reported association between SNPs in SNAP25 and ADHD, and controversial results were observed. In this study, we analyzed the possible association between six polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and rs362998) of SNAP25 and ADHD in a pooled sample of ten family-based studies and four case-control studies by using meta-analysis. The combined analysis results were significant only for rs3746544 (P = 0.010) with mild association (odds ratio (OR) = 1.14). And, the meta-analysis data for rs8636, rs362549, and rs362998 are the first time to be reported; however, no positive association was detected. In conclusion, we report some evidence supporting the association of SNAP25 to ADHD. Future research should emphasize genome-wide association studies in more specific subgroups and larger independent samples.

  20. Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis

    PubMed Central

    Weng, Hong; Li, Sheng; Huang, Jing-Yu; He, Zi-Qi; Meng, Xiang-Yu; Cao, Yue; Fang, Cheng; Zeng, Xian-Tao

    2017-01-01

    Although the association between CAG and GGN repeats in the androgen receptor gene and prostate cancer risk has been widely studied, it remains controversial from previous meta-analyses and narrative reviews. Therefore, we performed this meta-analysis to provide more precise estimates with sufficient power. A total of 51 publications with 61 studies for CAG repeats and 14 publications with 16 studies for GGN repeats were identified in the meta-analysis. The results showed that short CAG repeats (<22 repeats) carriers presented an elevated risk of prostate cancer than long CAG repeats (≥22) carriers (OR = 1.31, 95% CI 1.16 to 1.47). Prostate cancer cases presented an average fewer CAG repeats (MD = −0.85, 95% CI −1.28 to −0.42) than controls. Short GGN repeats (≤16) carriers presented an increased risk of prostate cancer than long GGN repeats (>16) carriers (OR = 1.38, 95% CI 1.05 to 1.82). In subgroup analyses, the abovementioned significant association was predominantly observed in Caucasian populations. The meta-analysis showed that short CAG and GGN repeats in androgen receptor gene were associated with increased risk of prostate cancer, especially in Caucasians. PMID:28091563

  1. Certain Polymorphisms in SP110 Gene Confer Susceptibility to Tuberculosis: A Comprehensive Review and Updated Meta-Analysis

    PubMed Central

    Zhang, Shuai; Wang, Xue-bin; Han, Ya-di; Wang, Chen; Zhou, Ye

    2017-01-01

    Purpose Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. Materials and Methods Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. Results The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. Conclusion Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB. PMID:27873510

  2. Identification of Single Nucleotide Polymorphisms and analysis of Linkage Disequilibrium in sunflower elite inbred lines using the candidate gene approach

    PubMed Central

    Fusari, Corina M; Lia, Verónica V; Hopp, H Esteban; Heinz, Ruth A; Paniego, Norma B

    2008-01-01

    Background Association analysis is a powerful tool to identify gene loci that may contribute to phenotypic variation. This includes the estimation of nucleotide diversity, the assessment of linkage disequilibrium structure (LD) and the evaluation of selection processes. Trait mapping by allele association requires a high-density map, which could be obtained by the addition of Single Nucleotide Polymorphisms (SNPs) and short insertion and/or deletions (indels) to SSR and AFLP genetic maps. Nucleotide diversity analysis of randomly selected candidate regions is a promising approach for the success of association analysis and fine mapping in the sunflower genome. Moreover, knowledge of the distance over which LD persists, in agronomically meaningful sunflower accessions, is important to establish the density of markers and the experimental design for association analysis. Results A set of 28 candidate genes related to biotic and abiotic stresses were studied in 19 sunflower inbred lines. A total of 14,348 bp of sequence alignment was analyzed per individual. In average, 1 SNP was found per 69 nucleotides and 38 indels were identified in the complete data set. The mean nucleotide polymorphism was moderate (θ = 0.0056), as expected for inbred materials. The number of haplotypes per region ranged from 1 to 9 (mean = 3.54 ± 1.88). Model-based population structure analysis allowed detection of admixed individuals within the set of accessions examined. Two putative gene pools were identified (G1 and G2), with a large proportion of the inbred lines being assigned to one of them (G1). Consistent with the absence of population sub-structuring, LD for G1 decayed more rapidly (r2 = 0.48 at 643 bp; trend line, pooled data) than the LD trend line for the entire set of 19 individuals (r2 = 0.64 for the same distance). Conclusion Knowledge about the patterns of diversity and the genetic relationships between breeding materials could be an invaluable aid in crop improvement

  3. Association between polymorphisms of the renin-angiotensin system genes and breast cancer risk: a meta-analysis.

    PubMed

    Xi, Bo; Zeng, Tao; Liu, Liu; Liang, Yajun; Liu, Weina; Hu, Yuehua; Li, Jun

    2011-11-01

    The renin-angiotensin system (RAS) has been considered to be implicated in the development of breast cancer. However, the results are inconsistent. In this study, we conducted a meta-analysis to assess the association between four polymorphisms, including angiotensin I-converting enzyme (ACE) I/D and A240T, angiotensin II type 1 receptor (AGTR1) A1166C and angiotensinogen (AGT) M235T polymorphisms, and breast cancer risk. Published literature from PubMed, ISI web of science, and Embase databases were retrieved. All studies evaluating the association between ACE I/D, ACE A240T, AGTR1 A1166C, or AGT M235T polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Ten studies (1,650 cases and 9,283 controls) on ACE I/D polymorphism, six studies (1,316 cases and 2,632 controls) on ACE A240T polymorphism, three studies (235 cases and 601 controls) on AGTR1 A1166C polymorphism, and two studies (273 cases and 3,547 controls) on AGT M235T polymorphism were included. Overall, the meta-analysis showed no significant association between I/D or A240T polymorphism and breast cancer risk in either genetic model. Further subgroup analysis by ethnicity also revealed non-significant association in Caucasian or Asian populations except for Africans (the statistically significant association for ACE I/D or A240T polymorphism in Africans derived from only one study). A marginally significant association was observed for AGTR1 A1166C polymorphism in Caucasians (CC vs. AA: OR = 0.31, 95% CI 0.10-0.99). In addition, there was a significant association between AGT M235T polymorphism and breast cancer risk in Caucasians (OR = 1.45, 95% CI 1.12-1.88). The present meta-analysis suggested that ACE I/D and A240T polymorphisms might not be a good predictor of breast cancer risk, while AGTR1 A1166C and AGT M235T polymorphisms might be implicated in the pathogenesis of breast cancer. Given the

  4. New single nucleotide polymorphisms (SNPs) in homologous recombination repair genes detected by microarray analysis in Polish breast cancer patients.

    PubMed

    Romanowicz, Hanna; Strapagiel, Dominik; Słomka, Marcin; Sobalska-Kwapis, Marta; Kępka, Ewa; Siewierska-Górska, Anna; Zadrożny, Marek; Bieńkiewicz, Jan; Smolarz, Beata

    2016-11-30

    Breast cancer is the most common cause of malignancy and mortality in women worldwide. This study aimed at localising homologous recombination repair (HR) genes and their chromosomal loci and correlating their nucleotide variants with susceptibility to breast cancer. In this study, authors analysed the association between single nucleotide polymorphisms (SNPs) in homologous recombination repair genes and the incidence of breast cancer in the population of Polish women. Blood samples from 94 breast cancer patients were analysed as test group. Individuals were recruited into the study at the Department of Oncological Surgery and Breast Diseases of the Institute of the Polish Mother's Memorial Hospital in Lodz, Poland. Healthy controls (n = 500) were obtained from the Biobank Laboratory, Department of Molecular Biophysics, University of Lodz. Then, DNA of breast cancer patients was compared with one of the disease-free women. The test was supported by microarray analysis. Statistically significant correlations were identified between breast cancer and 3 not described previously SNPs of homologous recombination repair genes BRCA1 and BRCA2: rs59004709, rs4986852 and rs1799950. Further studies on larger groups are warranted to support the hypothesis of correlation between the abovementioned genetic variants and breast cancer risk.

  5. The hOGG1 Ser326Cys gene polymorphism and susceptibility for bladder cancer: a meta-analysis

    PubMed Central

    Wenjuan, Cao; Jianzhong, Lu; Chong, Li; Yanjun, Gao; Keqing, Lu; Hanzhang, Wang; Zhiping, Wang

    2016-01-01

    ABSTRACT Objective: To assess the susceptibility of the hOGG1 genetic polymorphism for bladder cancer and evaluate the impact of smoking exposure. Materials and Methods: Articles included in PubMed, Medline and Springer databases were retrieved using the following key words: “human 8-oxoguanine DNA glycosylase”, “OGG”, “OGG1”, “hOGG1”, “genetic variation”, “polymorphism” , “bladder cancer”, and “bladder carcinoma” to Meta-analysis was performed to detect whether there were differences between the bladder cancer group and the control group about the distribution of genotypes of the hOGG1 gene. Results: The results showed that there are no significant associations between the hOGG1 326Cys polymorphism and bladder cancer: GG vs. CC (OR: 1.09, 95% CI: 0.85–1.40, p=0.480); GC vs. CC (OR: 1.05, 95% CI: 0.85–1.28, p=0.662); GG+GC vs. CC (OR: 1.04, 95% CI: 0.89–1.21, p=0.619); GG vs. GC+CC(OR: 1.02, 95% CI: 0.78–1.33, p=0.888); G vs. C (OR: 1.01, 95% CI: 0.91–1.13, p=0.818). In the smoker population, no significant associations between the hOGG1 326Cys polymorphism and bladder cancer were observed for all the models. However, individuals carrying the hOGG1 Cys326Cys genotype have increased risk for bladder cancer compared to those carrying the hOGG1 Ser326Ser genotype in the non-smoker Asian population. Conclusion: The hOGG1 326Cys polymorphisms aren't a risk factor for bladder cancer, especially in the smoker population. But GG genotype is a risk factor for bladder cancer to the non-smoker Asian population compared with CC genotype. PMID:27583352

  6. An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients

    PubMed Central

    2016-01-01

    Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed. PMID:27366014

  7. An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients.

    PubMed

    Park, Kui Young; Li, Kapsok; Seok, Joon; Seo, Seong Jun

    2016-07-01

    Research of the FLG mutation in various ethnic groups revealed non-overlapping mutation patterns. In addition, Japanese and Chinese atopic patients showed somewhat different mutations. These ethnic differences make the research on Korean patients mandatory; however, no systematic research on Korean atopic dermatitis (AD) patients has been performed. This study aims to investigate the genetic polymorphism of FLG in Korean atopic dermatitis patients. The study was made up of three groups including 9 Ichthyosis vulgaris (IV) patients, 50 AD patients and 55 normal controls: the ichthyosis group was incorporated due to the reported association between the FLG mutation and IV. In comparison to other sequencing methods, the overlapping long-range PCR was used. We revealed the genetic polymorphism of filaggrin in Koreans, and at the same time, we discovered nonsense mutations in p.Y1767X and p.K4022X in Korean AD patients. By using FLG sequencing techniques confirmed in this study, new mutations or genetic polymorphisms with ethnic characteristics would be detected and further larger studies of repeat number polymorphisms could be performed.

  8. Association analysis of single nucleotide polymorphisms in candidate genes with root traits in maize (Zea mays L.) seedlings.

    PubMed

    Kumar, Bharath; Abdel-Ghani, Adel H; Pace, Jordon; Reyes-Matamoros, Jenaro; Hochholdinger, Frank; Lübberstedt, Thomas

    2014-07-01

    Several genes involved in maize root development have been isolated. Identification of SNPs associated with root traits would enable the selection of maize lines with better root architecture that might help to improve N uptake, and consequently plant growth particularly under N deficient conditions. In the present study, an association study (AS) panel consisting of 74 maize inbred lines was screened for seedling root traits in 6, 10, and 14-day-old seedlings. Allele re-sequencing of candidate root genes Rtcl, Rth3, Rum1, and Rul1 was also carried out in the same AS panel lines. All four candidate genes displayed different levels of nucleotide diversity, haplotype diversity and linkage disequilibrium. Gene based association analyses were carried out between individual polymorphisms in candidate genes, and root traits measured in 6, 10, and 14-day-old maize seedlings. Association analyses revealed several polymorphisms within the Rtcl, Rth3, Rum1, and Rul1 genes associated with seedling root traits. Several nucleotide polymorphisms in Rtcl, Rth3, Rum1, and Rul1 were significantly (P<0.05) associated with seedling root traits in maize suggesting that all four tested genes are involved in the maize root development. Thus considerable allelic variation present in these root genes can be exploited for improving maize root characteristics.

  9. Association analysis of FTO gene polymorphisms with obesity in Greek adults.

    PubMed

    Goutzelas, Yiannis; Kotsa, Kalliopi; Vasilopoulos, Yiannis; Tsekmekidou, Xanthippi; Stamatis, Costas; Yovos, John G; Sarafidou, Theologia; Mamuris, Zissis

    2017-05-20

    Nowadays, obesity is the greatest scourge worldwide, particularly for the developed countries and is a huge burden for the public health. Over the past decade, GWAS have revealed a number of genes associated with obesity. The fat mass and obesity associated (FTO) gene was the first one associated with obesity in a significant number of populations and recent meta-analysis studies confirm this association. FTO is a N-methyladenosine demethylase and in addition to the genetic association, its biological role in the regulation of body weight has been documented. Due to lack of replication regarding FTO association with obesity in the Greek adult population, we analyzed three SNPs, i.e. rs9939609, rs9930506 and rs3751812 in a cohort of 203 adults, comprising of 95 obese, 58 overweight and 50 control individuals. Analysis has shown a significant association for FTO (rs9930506; A/G) 'G' allele with obesity and a difference by 3.2 BMI units between the two homozygotes (AA versus GG). This association, which was detected for the first time in this population, suggests that FTO rs9930506 is a predisposition marker to obesity in the Greek adults, but the results should be taken cautiously due to the limitation of the relatively small sample size of the subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Sequence analysis of three canine adipokine genes revealed an association between TNF polymorphisms and obesity in Labrador dogs.

    PubMed

    Mankowska, M; Stachowiak, M; Graczyk, A; Ciazynska, P; Gogulski, M; Nizanski, W; Switonski, M

    2016-04-01

    Obesity is an emerging health problem in purebred dogs. Due to their crucial role in energy homeostasis control, genes encoding adipokines are considered candidate genes, and their variants may be associated with predisposition to obesity. Searching for polymorphism was carried out in three adipokine genes (TNF, RETN and IL6). The study was performed on 260 dogs, including lean (n = 109), overweight (n = 88) and obese (n = 63) dogs. The largest cohort was represented by Labrador Retrievers (n = 136). Altogether, 24 novel polymorphisms were identified: 12 in TNF (including one missense SNP), eight in RETN (including one missense SNP) and four in IL6. Distributions of five common SNPs (two in TNF, two in RETN and one in IL6) were further analyzed with regard to body condition score. Two SNPs in the non-coding parts of TNF (c.-40A>C and c.233+14G>A) were associated with obesity in Labrador dogs. The obtained results showed that the studied adipokine genes are highly polymorphic and two polymorphisms in the TNF gene may be considered as markers predisposing Labrador dogs to obesity. © 2015 Stichting International Foundation for Animal Genetics.

  11. "Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis".

    PubMed

    Yadav, Upendra; Kumar, Pradeep; Yadav, Sushil Kumar; Mishra, Om Prakash; Rai, Vandana

    2015-02-01

    Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC) = 1.43; 95% CI: 1.05-1.94), European (OR(TvsC) = 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC) = 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD.

  12. Associations between two polymorphisms (FokI and BsmI) of vitamin D receptor gene and type 1 diabetes mellitus in Asian population: a meta-analysis.

    PubMed

    Wang, Guofeng; Zhang, Qingqing; Xu, Ning; Xu, Kuanfeng; Wang, Jian; He, Wei; Yang, Tao

    2014-01-01

    Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 1 diabetes mellitus (T1DM). However, the results to date have been inconclusive. We performed a meta-analysis to examine the association between 2 polymorphisms (FokI and BsmI) of the VDR gene and T1DM in the Asian population. Literature was retrieved from PubMed, Web of Science, CBM, Embase and Chinese databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model. In total, 20 papers (BsmI: 13 studies; FokI: 13 studies) were included. In contrast to the FokI polymorphism, the BsmI polymorphism was associated with an increased risk of T1DM in the Asian population (OR = 1.47, 95% CI = 1.13-1.91, P = 0.004 for B vs. b). Upon stratification by regional geography, an increased risk of T1DM in association with the BsmI polymorphism was observed in the East Asian population (OR = 1.97, 95% CI = 1.38-2.83, P<0.001 for B vs. b), whereas the FokI polymorphism was associated with an increased risk of T1DM in the West Asian population (OR = 1.45, 95% CI = 1.12-1.88, P = 0.004 for F vs. f). Our meta-analysis suggests that the BsmI polymorphism may be a risk factor for susceptibility to T1DM in the East Asian population, and the FokI polymorphism is associated with an increased risk of T1DM in the West Asian population. However, because the study size was limited, further studies are essential to confirm our results.

  13. CYP11B2 T-344C Gene Polymorphism and Atrial Fibrillation: A Meta-Analysis of 2,758 Subjects

    PubMed Central

    Li, Yan-yan; Zhou, Chuan-wei; Xu, Jian; Qian, Yun; Wang, Bei

    2012-01-01

    Background Aldosterone synthase (CYP11B2) T-344C gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. However, the results of individual studies remain conflicting. Objective and methods A meta-analysis including 2,758 subjects from six individual studies was performed to explore the correlation between CYP11B2 T-344C gene polymorphisms and AF. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by the fixed– or random–effects model. Results A significant relationship between CYP11B2 T-344C gene polymorphism and AF was found under allelic (OR: 1.26, 95% CI: 1.11–1.42, P = 0.0002), recessive (OR: 1.99, 95% CI: 1.26–3.14, P = 0.003), dominant (OR: 0.903, 95% CI: 0.820–0.994, P = 0.036), homozygous (OR: 1.356, 95% CI: 1.130–1.628, P = 0.001), and additive (OR: 1.153, 95% CI: 1.070–1.243, P = 1.0×10−10) genetic models. No significant association between CYP11B2 T-344C gene polymorphism and AF was found under the heterozygous genetic model (OR: 1.040, 95% CI: 0.956–1.131, P = 0.361). Conclusions A significant association was found between CYP11B2 T-344C gene polymorphism and AF risk. Individuals with the C allele of CYP11B2 T-344C gene polymorphism have higher risk for AF. PMID:23209837

  14. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences.

  15. Association of estrogen receptor gene polymorphisms with human precocious puberty: a systematic review and meta-analysis.

    PubMed

    Luo, Yan; Liu, Qin; Lei, Xun; Wen, Yi; Yang, Ya-Lan; Zhang, Rui; Hu, Meng-Yao

    2015-07-01

    This study aims to estimate the association between ESR1 polymorphisms (PvuII and XbaI) and ESR2 polymorphisms (RsaI and AluI) with precocious puberty. Relevant studies published before March 2014 were retrieved by a electronic search among nine databases. Meta-analysis of the pooled odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. Four eligible case-control studies including 491 precocious puberty patients and 370 healthy controls were identified. Three studies reported ESR1 PvuII and XbaI polymorphism and one study reported ESR2 RsaI and AluI polymorphism. Increment of precocious puberty risk was associated with PvuII polymorphism in the heterosis model ((CT) versus TT: OR 1.42, 95% CI: 1.05-1.91, p = 0.02). Risk of precocious puberty was associated with XbaI polymorphism in the dominant model (GG + GA versus AA: OR 1.48, 95% CI: 1.11-1.97, p = 0.007) and the heterosis model (GA versus AA: OR 1.68, 95% CI: 1.23-2.29, p = 0.001). This meta-analysis suggests that ESR1 XbaI and PvuII polymorphisms are associated with precocious puberty susceptibility, and the relationship between ESR2 RsaI and AluI polymorphism with precocious puberty remains to be further investigated. Well-designed studies with large sample size among different polymorphisms and ethnicities are in urgent need to provide and update reliable data for comprehensive and definite conclusion.

  16. Estrogen receptor-alpha gene PvuII (T/C) and XbaI (A/G) polymorphisms and endometriosis risk: a meta-analysis.

    PubMed

    Li, Ya; Liu, Fei; Tan, Shi-Qiao; Wang, Yan; Li, Shang-Wei

    2012-10-15

    Estrogen receptor-alpha (ER-α) polymorphisms have been hypothesized to be associated with the risk of endometriosis (EMT) development by many epidemiological studies, however, the available results were conflicting. To derive a more precise estimation of association between the ER-α PvuII (T/C) and XbaI (A/G) polymorphisms and risk of EMT, we performed a meta-analysis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for ER-α polymorphisms and EMT were calculated in a fixed-effects model and a random-effects model when appropriate. This meta-analysis included 20 case-control studies with 1752 cases and 1742 controls for PvuII polymorphism and 15 case-control studies with 1349 cases and 1411 controls for XbaI polymorphism. For PvuII T/C polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, a significantly increased risk was observed among Caucasians (recessive model, OR=2.56, 95% CI=1.06-6.16) and among studies without the HWE (recessive model, OR=1.85, 95% CI=1.20-2.84). For XbaI A/G polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, still no obvious associations were found. No publication bias was found in the present study. This meta-analysis suggests that ER-α gene PvuII (T/C) and XbaI (A/G) polymorphisms may not be associated with EMT risk, while the observed increase in risk of EMT may be due to small-study bias. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Relationship between PPARγ Pro12Ala gene polymorphism and type 2 diabetic nephropathy risk in Asian population: results from a meta-analysis.

    PubMed

    Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen; Yuan, Fei; Li, Yi; Hu, Haoqiang; Chen, Zijun

    2014-04-01

    The relationship between peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala gene polymorphism and type 2 diabetic nephropathy (T2DN) risk in Asians is still unclear. This study was performed to evaluate if there was an association between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 October 2013, and eligible studies were included and synthesized. Ten reports were recruited into this meta-analysis for the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk. The Pro12Ala gene polymorphism in the Asian population was shown to be not associated with T2DN risk (Ala/Ala: OR = 0.67, 95% CI: 0.22-2.00, p = 0.47; Pro/Pro: OR = 1.77, 95% CI: 0.82-1.65, p = 0.39; Ala allele: OR = 0.74, 95% CI: 0.47-1.16, p = 0.19). In the sensitivity analysis according to Hardy-Weinberg equilibrium (HWE), the control source from hospital, the control source from population, the genotyping methods using PCR-RFLP, the genotyping methods using Taqman, sample size of case (≥ 100), the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk was also not found. Interestingly, in the sensitivity analysis according to sample size of case (<100), Ala allele was associated with T2DN risk, but not the Pro/Pro genotype. However, the sample size for sensitivity analysis according to sample size of case (<100) was relatively small and therefore, the results should be interpreted with care. In conclusion, the PPARγ Pro12Ala gene polymorphism was not associated with T2DN risk in Asians. However, Ala allele was associated with T2DN risk when the sample size of case was less than 100. Nonetheless, additional studies are required to firmly establish a correlation between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians.

  18. Analysis of matrix metalloproteinase-1 gene polymorphisms and expression in benign and malignant breast tumors

    PubMed Central

    Zhou, Jing; Brinckerhoff, Constance; Lubert, Susan; Yang, Kui; Saini, Jasmine; Hooke, Jeffrey; Mural, Richard; Shriver, Craig; Somiari, Stella

    2013-01-01

    A guanine insertion polymorphism in matrix metalloproteinase-1 promoter (MMP-1 2G) is linked to early onset and aggressiveness in cancer. We determined the role of MMP-1 2G on the level of MMP-1 expression and breast cancer severity in benign breast disease, atypical hyperplasia, invasive and non invasive (in situ) breast cancer. We observed no significant difference in genotype distribution among the different breast disease groups. However, the level of MMP-1 expression was significantly higher in atypical ductal hyperplasia compared to benign breast disease; and in invasive breast cancer compared to in situ breast cancer. MMP-1 2G insertion polymorphism in the invasive group also correlated significantly with the expression of MMP-1 and breast cancer prognostic markers HER2 and P53. PMID:22011282

  19. Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis.

    PubMed

    Li, Hui; Fu, Wei-Ping; Hong, Ze-Hui

    2013-03-01

    Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD). Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. However, the conclusions were controversial. We performed a comprehensive meta-analysis to clarify these findings. A total of 24 studies comprising 8,259 COPD patients and 42,883 controls were included. The overall results showed that the EPHX1 113 mutant homozygote was significantly associated with an increased risk of COPD (OR, 1.33; 95% CI, 1.06-1.69). The subgroup analyses demonstrated this association in Caucasian individuals (OR, 1.61; 95% CI, 1.12-2.31) but not in Asian individuals. The 139 mutant heterozygote was significantly associated with a decreased risk of COPD in Asian populations (OR, 0.82; 95% CI, 0.68-0.99) but not in Caucasian populations. Pooled analyses revealed that the extremely slow (OR, 1.77; 95% CI, 1.23-2.55) and slow EPHX1 enzyme activity (OR, 1.44; 95% CI, 1.13-1.85) were associated with an increased risk of COPD, while the fast enzyme activity was not associated with a decreased risk of COPD. The stratified analysis demonstrated this association in Caucasian but not in Asian individuals. Furthermore, a modest difference in the risk of COPD was observed between the subgroups by using the cigarette smokers or the non-smokers as controls. A significant correlation between the two functional polymorphisms, T113C and A139G, of the EPHX1 gene and the enzyme activity and the individual's susceptibility to COPD was noted. In addition, the results supported a contribution of EPHX1 to the aetiology of COPD.

  20. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    SciTech Connect

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  1. Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism and Risk of Schizophrenia: A Meta-analysis of Case-Control Studies.

    PubMed

    Kheirollahi, Majid; Kazemi, Elahe; Ashouri, Saeideh

    2016-01-01

    According to evidences from previous family and association studies, it has been claimed that genetic factors are involved in the neuropathogenesis of Schizophrenia disorder. Whether the Val66Met variant of brain-derived neurotrophic factor (BDNF) gene plays any roles in the pathogenesis of this syndrome or could be a potential biomarker for prognosis of this disorder has been a long-standing controversial issue. We performed a meta-analysis restricted to case-control studies and searched Pubmed, PsychInfo, and Google scholar using keywords including 'association,' 'Val66Met,' 'BDNF,' and 'schizophrenia' published up to May 1, 2015. A total of 39 studies for schizophrenia were combined by fixed- and random-effects models. The pooled results from the schizophrenia sample indicated no significant evidence for the association of Val/Val and Val/Met genotypes of BDNF gene with schizophrenia, but it was observed that there is an association between Met/Met polymorphism and schizophrenia in Asian, European, and Chinese populations, this means that the risk of schizophrenia in Asian, European, and Chinese populations with Met/Met genotype is, respectively, 9, 26, and 9%. There was a significant association between BDNF Val66Met polymorphism and schizophrenia in our meta-analysis study. We cannot rule out the possibility that other polymorphisms in the BDNF gene are involved in the pathophysiology of schizophrenia. In addition, more studies should be conducted on the polymorphisms in other genes to elucidate their possible roles in schizophrenia.

  2. Relationship Between Interleukin-10 Gene C-819T Polymorphism and Gastric Cancer Risk: Insights From a Meta-Analysis.

    PubMed

    Cui, Xigang; Huang, Qingxian; Li, Xianglin; Liu, Fang; Wang, Dan; Yan, Dong; Wang, Bin; Yang, Chunhua; Mi, Jia; Tian, Geng

    2016-08-12

    BACKGROUND As a pleiotropic cytokine, interleukin-10 (IL-10) plays a regulatory role in carcinogenesis and tumor growth. The aim of this meta-analysis was to assess the susceptibility of the IL-10 gene C-819T polymorphism to gastric cancer. MATERIAL AND METHODS Study identification and data extraction were independently completed by 2 authors. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated and summarized. RESULTS In total, 11 articles including 1960 gastric cancer patients and 3705 controls were qualified. Overall analyses revealed a 13% reduced risk of gastric cancer conferred by the -819T allele relative to the -819C allele (OR=0.87; 95% CI: 0.77-0.97; P=0.016), without heterogeneity (I2=35.1%). In subgroup analyses, a significant difference was identified in East Asian populations (OR=0.85; 95% CI: 0.73-0.98; P=0.029, I2=43.6%), for gastric adenocarcinoma (OR=0.80; 95% CI: 0.66-0.96; P=0.017, I2=0.0%), and in population-based studies (OR=0.81; 95% CI: 0.70-0.93; P=0.003, I2=0.0%). The visual funnel plots and Egger's tests suggested no evidence of publication bias. CONCLUSIONS Extending previous findings, we demonstrate a protective role of the IL-10 gene -819T allele in susceptibility to gastric cancer, and this role was more evident for gastric adenocarcinoma.

  3. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer.

    PubMed

    Spink, Barbara C; Bloom, Michael S; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n=2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n=4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility.

  4. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    PubMed Central

    Spink, Barbara C.; Bloom, Michael S.; Wu, Susan; Sell, Stewart; Schneider, Erasmus; Ding, Xinxin; Spink, David C.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC)n, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC)2 alleles were observed; however, in western gorilla, (GGGGC)n alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC)n was n = 4>5≫2, 6. When frequencies of the (GGGGC)n alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC)2 was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC)n short tandem repeats are inherited, and that the (GGGGC)2 allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. PMID:25447411

  5. Segregation of yeast polymorphic STA genes in meiotic recombinants and analysis of glucoamylase production.

    PubMed

    Balogh, I; Maráz, A

    1996-12-01

    Hybrid yeast strains were constructed using haploid Saccharomyces cerevisiae and Saccharomyces cerevisiae var. diastaticus strains to get haploid meiotic recombinants having more than one copy of STA1, STA2, and STA3 genes. STA genes were localized on the chromosomes by pulsed field gel electrophoresis. Working gene dosage effects were found among STA genes in liquid starch medium, indicating low levels of glucose repression. Growth of strains, however, was not influenced by their STA copy number.

  6. Significant associations between the A163G and G1181C polymorphisms of the osteoprotegerin gene and risk of osteoporosis, especially in postmenopausal women: a meta-analysis.

    PubMed

    Luo, Yi; Hu, Zhenming; Hao, Jie; Jiang, Wei; Shen, Jieliang; Zhao, Jun

    2014-03-01

    Whereas some studies have reported that the osteoprotegerin (OPG) gene is associated with osteoporosis risk in some studies, their results have proved inconclusive. We performed a meta-analysis of studies on the associations between OPG A163G and G1181C polymorphisms and the risk of osteoporosis. A literature search in PubMed, Embase, Web of Science, Cochrane Library, and China Biological Medicine (CBM) databases was conducted to identify all eligible case-control studies published before August 15th, 2013. Pooled odds ratios with their corresponding 95% confidence intervals were used to evaluate the strength of the association under either a fixed- or random-effect model according to the heterogeneity test. Ten case-control studies were included with a total of 1673 osteoporosis cases and 1554 healthy controls in this meta-analysis. For the OPG A163G polymorphism, the combined results showed that the G allele of the A163G polymorphism may be associated with an increased risk of osteoporosis. Stratified analyses showed that the magnitude of the effect was similar among the Caucasian and postmenopausal women subgroups. Unlike the A163G polymorphism, the meta-analysis results revealed that the C allele of the G1181C polymorphism may be associated with a decreased risk of osteoporosis, especially in the Asian and postmenopausal women subgroups. No publication bias was detected for either polymorphism. Our findings showed that the G allele of the OPG A163G polymorphism may increase osteoporosis risk, whereas the C allele of the G1181C polymorphism may protect individuals from osteoporosis. Both of these effects were observed in postmenopausal women.

  7. Mannose-binding lectin codon 54 gene polymorphism and vulvovaginal candidiasis: a systematic review and meta-analysis.

    PubMed

    Nedovic, Bojan; Posteraro, Brunella; Leoncini, Emanuele; Ruggeri, Alberto; Amore, Rosarita; Sanguinetti, Maurizio; Ricciardi, Walter; Boccia, Stefania

    2014-01-01

    Mannose-binding lectin (MBL) plays a key role in the human innate immune response. It has been shown that polymorphisms in the MBL2 gene, particularly at codon 54 (variant allele B; wild-type allele designated as A), impact upon host susceptibility to Candida infection. This systematic review and meta-analysis were performed to assess the association between MBL2 codon 54 genotype and vulvovaginal candidiasis (VVC) or recurrent VVC (RVVC). Studies were searched in MEDLINE, SCOPUS, and ISI Web of Science until April 2013. Five studies including 704 women (386 cases and 318 controls) were part of the meta-analysis, and pooled ORs were calculated using the random effects model. For subjects with RVVC, ORs of AB versus AA and of BB versus AA were 4.84 (95% CI 2.10-11.15; P for heterogeneity = 0.013; I(2) = 68.6%) and 12.68 (95% CI 3.74-42.92; P for heterogeneity = 0.932, I(2) = 0.0%), respectively. For subjects with VVC, OR of AB versus AA was 2.57 (95% CI 1.29-5.12; P for heterogeneity = 0.897; I (2) = 0.0%). This analysis indicates that heterozygosity for the MBL2 allele B increases significantly the risk for both diseases, suggesting that MBL may influence the women's innate immunity in response to Candida.

  8. Is the Val66Met polymorphism of the brain-derived neurotrophic factor gene associated with panic disorder? A meta-analysis.

    PubMed

    Chen, Kaiyuan; Wang, Na; Zhang, Jie; Hong, Xiaohong; Xu, Haiyun; Zhao, Xiaofeng; Huang, Qingjun

    2017-06-01

    Although emerging evidence has suggested an association between the Val66Met (rs6265) polymorphisms in brain-derived neurotrophic factor (BDNF) gene and the panic disorder, the conclusion is inclusive given the mixed results. This meta-analysis reviewed and analyzed the recent studies addressing the potential association between the Val66Met polymorphisms and panic disorder susceptibility. Related case-control studies were retrieved by database searching and selected according to established inclusion criteria. Six articles were identified, which explored the association between the BDNF Val66Met polymorphism and panic disorder. Statistical analyses revealed no association for the allele contrast and the dominant model. However, the recessive model showed a significant association between the BDNF Val66Met polymorphism and panic disorder (odds ratio = 1.26, 95% confidence interval = 1.04-1.52, z = 2.39, P = 0.02). Despite of some limitations, this meta-analysis suggests that the Val66Met polymorphism of BDNF gene is a susceptibility factor for panic disorder. © 2015 Wiley Publishing Asia Pty Ltd.

  9. Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol.

    PubMed

    Gong, Shaoqing; Xu, Chun; Wang, Liang; Liu, Ying; Owusu, Daniel; Bailey, Beth A; Li, Yujing; Wang, Kesheng

    2017-04-01

    The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level. Multiple logistic regression model and linear regression model were used to examine the associations of 259 single nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity and T2D as binary traits, and HDL level as a continuous trait using the Marshfield data, respectively. A replication study of obesity was conducted using the Health Aging and Body Composition (Health ABC) sample. 23SNPs were associated with obesity (p<0.05) in the Marshfield sample and rs4921966 revealed the strongest association (p=3.97×10(-6)). Of the 23SNPs, 20 were significantly associated with obesity in the meta-analysis of two samples (p<0.05). Furthermore, 6SNPs revealed associations with T2D in the Marshfield data (top SNP rs12156368 with p=3.05×10(-3)); while two SNPs (rs6983992 and rs7843239) were associated with both obesity and T2D (p=0.0188 and 0.023 for obesity and p=8.47×10(-3) and 0.0128 for T2D, respectively). Furthermore, 11SNPs revealed associations with HDL level (top SNP rs13254772 with p=2.79×10(-3)) in the Marshfield data; meanwhile rs7009615 was associated with both T2D (p=0.038) and HDL level (p=4.44×10(-3)). In addition, haplotype analyses further supported the results of single SNP analysis. Common variants in PSD3 were associated with obesity, T2D and HDL level. These findings add important new insights into the pathogenesis of obesity, T2D and HDL cholesterol. Published by Elsevier B.V.

  10. PRISMA-combined Myeloperoxidase -463G/A gene polymorphism and coronary artery disease: A meta-analysis of 4744 subjects.

    PubMed

    Li, Yan-Yan; Wang, Hui; Qian, Jin; Kim, Hyun Jun; Wu, Jing-Jing; Wang, Lian-Sheng; Zhou, Chuan-Wei; Yang, Zhi-Jian; Lu, Xin-Zheng

    2017-03-01

    Myeloperoxidase (MPO) -463G/A gene polymorphism may be associated with an increased risk of developing coronary artery disease (CAD). Studies on the subject, however, do not provide a clear consensus. This meta-analysis was performed to explore the relationship between MPO gene -463G/A polymorphism and CAD risk. This meta-analysis combines data from 4744 subjects from 9 independent studies. By using fixed or random effect models, the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were assessed. Our analysis found a significant association between MPO gene -463G/A polymorphism and CAD in the whole population under all genetic models: allelic (OR: 0.68, 95% CI: 0.54-0.85, P = 0.0009), recessive (OR: 0.41, 95% CI: 0.22-0.76, P = 0.005), dominant (OR: 0.682, 95% CI: 0.534-0.871, P = 0.002), homozygous (OR: 0.36, 95% CI: 0.16-0.79, P = 0.01), heterozygous genetic model (OR: 0.832, 95% CI: 0.733-0.945, P = 0.004), and additive (OR: 0.64, 95% CI: 0.46-0.90, P = 0.01), especially in the Chinese subgroup (P < 0.05). On the contrary, we found no such relationship in the non-Chinese subgroup (P > 0.05). The MPO gene -463G/A polymorphism is associated with CAD risk, especially within the Chinese population. The A allele of MPO gene -463G/A polymorphism might protect the people from suffering the CAD risk.

  11. Geographical and Ethnic Distributions of the MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in Chinese Populations: A Meta-Analysis.

    PubMed

    Wang, Xingmin; Fu, Jinjian; Li, Qianxi; Zeng, Dingyuan

    2016-01-01

    The geographical and ethnic distributions of the polymorphic methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and methionine synthase reductase (MTRR) mutation (A66G) remain heterogeneous in China. The goal of this study was to estimate the pooled frequencies of the alleles and associated genotypes of these gene polymorphisms among healthy populations in Mainland China. We systematically reviewed published epidemiological studies on the distributions of 3 genetic variants in Chinese healthy populations living in Mainland China through a meta-analysis. The relevant electronic databases were searched. All of the raw data of the eligible citations were extracted. The frequency estimates were stratified by geography, ethnicity and sex. Sixty-six studies were identified with a total of 92277 study participants. The meta-analysis revealed that the frequencies of the MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients. The frequencies of the 677T allele and 677TT genotype increased along the southern-central-northern direction across Mainland China (all Pvalues≤0.001). The frequencies of the 1298C, 1298CC, 66G and 66GG genotypes decreased along the south-central-north direction across the country (all Pvalues≤0.001). Our meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations.

  12. A critical analysis of disease-associated DNA polymorphisms in the genes of cattle, goat, sheep, and pig.

    PubMed

    Ibeagha-Awemu, Eveline M; Kgwatalala, Patrick; Ibeagha, Aloysius E; Zhao, Xin

    2008-04-01

    Genetic variations through their effects on gene expression and protein function underlie disease susceptibility in farm animal species. The variations are in the form of single nucleotide polymorphisms, deletions/insertions of nucleotides or whole genes, gene or whole chromosomal rearrangements, gene duplications, and copy number polymorphisms or variants. They exert varying degrees of effects on gene action, such as substitution of an amino acid for another, shift in reading frame and premature termination of translation, and complete deletion of entire exon(s) or gene(s) in diseased individuals. These factors influence gene function by affecting mRNA splicing pattern or by altering/eliminating protein function. Elucidating the genetic bases of diseases under the control of many genes is very challenging, and it is compounded by several factors, including host x pathogen x environment interactions. In this review, the genetic variations that underlie several diseases of livestock (under monogenic and polygenic control) are analyzed. Also, factors hampering research efforts toward identification of genetic influences on animal disease identification and control are highlighted. A better understanding of the factors analyzed could be better harnessed to effectively identify and control, genetically, livestock diseases. Finally, genetic control of animal diseases can reduce the costs associated with diseases, improve animal welfare, and provide healthy animal products to consumers, and should be given more attention.

  13. Single-nucleotide polymorphisms and activity analysis of the promoter and enhancer of the pig lactase gene.

    PubMed

    Du, Hai-Ting; Zhu, Hong-Yan; Wang, Jia-Mei; Zhao, Wei; Tao, Xiao-Li; Ba, Cai-Feng; Tian, Yu-Min; Su, Yu-Hong

    2014-07-15

    Lactose intolerance in northern Europeans is strongly associated with a single-nucleotide polymorphism (SNP) located 14 kb upstream of the human lactase gene: -13,910 C/T. We examined whether SNPs in the 5' flanking region of the pig lactase gene are similar to those in the human gene and whether these polymorphisms play a functional role in regulating pig lactase gene expression. The 5' flanking region of the lactase gene from several different breeds of pigs was cloned and analyzed for gene regulatory activity of a luciferase reporter gene. One SNP was found in the enhancer region (-797 G/A) and two were found in the promoter region (-308G/C and -301 A/G). The promoter C-308,G-301(Pro-CG) strongly promotes the expression of the lactase gene, but the promoter G-308,A-301(Pro-GA) does not. The enhancer A-797(Enh-A) genotype for Pro-GA can significantly enhance promoter activity, but has an inhibitory effect on Pro-CG. The Enhancer G-797(Enh-G) has a significant inhibitory effect on both promoters. In conclusion, the order of effectiveness on the pig lactase gene is Enh-A+Pro-GA>Enh-A/G+Pro-CG>Enh-G+Pro-GA. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The Analysis of Polymorphism of Alcohol Dehydrogenase 3 (ADH3) Gene and Influence of Liver Function Status in Indonesia.

    PubMed

    Suhartini; Mustofa; Nurhantari, Yudha; Rianto, Bambang Udji Djoko

    2017-01-31

    Indonesian culture actually has no historical record of behaviors in consuming alcohol, but there are many recent reports of alcohol abuse among Asian people involving their traditional drink. In genotype studies, the damage of the liver caused by consuming alcohol is influenced by the presence of the polymorphism enzyme gene. The lack of study regarding such topic is a signal to further investigate ADH3 gene distribution and its effect on liver function status. The total of 197 research subjects of Javanese descent received alcohol dehydrogenase 3 (ADH3) genetic polymorphism and liver status tests in the city of Yogyakarta, Indonesian. An analytical study with a cross-sectional design was then conducted on the subjects, with the resulting isolated DNAs amplified through polymerase chain reaction (PCR). The genotype of ADH3 was determined by means of restriction fragment length polymorphism (RFLP) using Ssp1 restricting enzyme. Liver function status was assessed by measuring serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and gamma glutamyl transferase (GGT) using a photometric system. Gene types of ADH3*1 (2.1%), ADH3*2 (82.7%) and ADH3*1/3*2 (15.2%) on the subjects were concluded, finding that there is no difference between the gender. In conclusion most of the ADH3 gene polymorphism of the subjects were ADH3*2 (82.7%). The influence of genetic polymorphisms on the status of liver function in the subjects showed significant difference according to GGT measurement, but the same cannot be said on the other two values measuring SGOT and SGPT.

  15. Association between the rs112735431 polymorphism of the RNF213 gene and moyamoya disease: A case-control study and meta-analysis.

    PubMed

    Huang, Yanlan; Cheng, Daobin; Zhang, Jiede; Zhao, Weijia

    2016-10-01

    Ring finger protein 213 (RNF213) gene polymorphisms are thought to be significant in the etiology and pathogenesis of moyamoya disease (MMD). Due to the rarity of MMD patients, their ethnic diversity, and the use of varying methodologies, studies of the association between these polymorphisms and MMD have not been repeatable. This lack of reproducibility affects the strength of the conclusions drawn from their results. We conducted the present case-control study and meta-analysis to provide more precise estimates of the association between the rs112735431 (c.14576G>A) polymorphism and the risk of MMD. A total of 81 MMD patients and 100 healthy controls were enrolled in our case-control study. The RNF213 rs112735431 (c.14576G>A) polymorphism was genotyped using Sanger sequencing after amplification with polymerase chain reaction (PCR). The genetic algorithm (GA) genotype and A allele frequencies of RNF213 rs112735431 (c.14576G>A) (odds ratio, OR=7.10, 95% confidence interval, CI=1.51-33.43, p=0.006; OR=9.37, 95% CI=2.10-41.84, p<0.001, respectively) were significantly higher in the MMD group than those in the control group. In our meta-analysis, we assessed a total of eight case-control studies, including 985 patients and 2335 controls. Pooled ORs indicated a significant association between the presence of the rs112735431 (c.14576G>A) polymorphism and MMD risk (dominant model: OR=74.55, 95% CI=35.86-154.98, p<0.00001). Subgroup analysis based on country and sensitivity analysis verified these results. Our case-control study and meta-analysis both provide evidence of an association between the rs112735431(c.14576G>A) polymorphism in the RNF213 gene and MMD risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Analysis of apoB gene polymorphism in control sample and group of patients with coronary heart disease from Moscow

    SciTech Connect

    Slominsky, P.A.; Shadrina, M.I.; Pogoda, T.V.

    1994-09-01

    We have analyzed two polymorphic regions of the apo B gene (5{prime} (CA)n microsatellite and insertion/deletion polymorphisms) in a random control sample and coronary heart disease (CHD) patients from Moscow. For this purpose we have used PCR technique followed by high-resolution PAGE. In the control sample only 3 different allelic variants of the 5{prime} minisatellite existed with 14 (frequency 70,7%), 15 (26,8%) and 16 (2.5%) CA repeats. In the patient`s group, allelic variants were also found with 13 CA repeats, but the frequency was very low (2.5%). However, we did not reveal any significant differences in allele and genotype distributions of insertion/deletion polymorphisms in the control group and the group of CHD patients (insertion frequency 67.9% and 62.5%, respectively).

  17. Comparison of PCR-based restriction length polymorphism analysis of urease genes with rRNA gene profiling for monitoring Helicobacter pylori infections in patients on triple therapy.

    PubMed Central

    Owen, R J; Bickley, J; Hurtado, A; Fraser, A; Pounder, R E

    1994-01-01

    Multiple isolates of Helicobacter pylori from antral biopsies of nine patients were examined by DNA fingerprinting. Analysis of rRNA gene patterns and HaeIII restriction fragment length polymorphism of PCR-amplified urease genes were compared and used to study colonization before and after failed triple therapy. H. pylori isolates from a single biopsy shared the same HaeIII DNA fingerprint regardless of the isolation method (plate or broth). DNA pattern types of paired strains of H. pylori were distinct between patients and were not grossly affected by treatment except for one patient with an altered strain type. H. pylori infections were generally associated with several subpopulations of strains, evident from the subtypic variation before and after treatment, detectable by both DNA fingerprinting methods. The urease gene patterns also provided evidence that some cultures of H. pylori probably contained a mixture of genomic subtypes. The study suggests that triple therapy has the effect either of inducing minor genomic variations or of changing the proportions of different subtypes of H. pylori. It was concluded that urease gene profiling provides a simple yet reliable method of establishing whether treatment failures are attributable to incomplete eradication of H. pylori. Images PMID:7914204

  18. Gene polymorphisms and chronic obstructive pulmonary disease.

    PubMed

    Wu, Xiaodan; Yuan, Bowei; López, Elena; Bai, Chunxue; Wang, Xiangdong

    2014-01-01

    The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.

  19. Characterization of Erwinia chrysanthemi by pectinolytic isozyme polymorphism and restriction fragment length polymorphism analysis of PCR-amplified fragments of pel genes.

    PubMed Central

    Nassar, A; Darrasse, A; Lemattre, M; Kotoujansky, A; Dervin, C; Vedel, R; Bertheau, Y

    1996-01-01

    Conserved regions about 420 bp long of the pelADE cluster specific to Erwinia chrysanthemi were amplified by PCR and used to differentiate 78 strains of E. chrysanthemi that were obtained from different hosts and geographical areas. No PCR products were obtained from DNA samples extracted from other pectinolytic and nonpectinolytic species and genera. The pel fragments amplified from the E. chrysanthemi strains studied were compared by performing a restriction fragment length polymorphism (RFLP) analysis. On the basis of similarity coefficients derived from the RFLP analysis, the strains were separated into 16 PCR RFLP patterns grouped in six clusters, These clusters appeared to be correlated with other infraspecific levels of E. chrysanthemi classification, such as pathovar and biovar, and occasionally with geographical origin. Moreover, the clusters correlated well with the polymorphism of pectate lyase and pectin methylesterase isoenzymes. While the pectin methylesterase profiles correlated with host monocot-dicot classification, the pectate lyase polymorphism might reflect the cell wall microdomains of the plants belonging to these classes. PMID:8779560

  20. Direct genotyping of Toxoplasma gondii from amniotic fluids based on B1 gene polymorphism using minisequencing analysis

    PubMed Central

    2013-01-01

    Background Because some Toxoplasma gondii genotypes may be more virulent in pregnant women, discriminating between them appears valuable. Currently, the main genotyping method is based on single copy microsatellite markers, which limit direct genotyping from amniotic fluids (AFs) to samples with a high parasitic load. We investigated whether the multicopy gene B1 could type the parasite with a higher sensitivity. To estimate the amplifiable DNA present in AFs, we first compared three different PCR assays used for Toxoplasma infection diagnosis: the P30-PCR, targeting the single copy gene P30; the B1-PCR, targeting the repeated B1 gene; and RE-PCR, targeting the repeated element. Results Of the 1792 AFs analyzed between 2008 and 2011, 73 were RE-PCR positive. Of those, 49 (67.1%) were P30-PCR and B1-PCR positive, and 14 (19.2%) additional AFs were B1-PCR positive only. All 63 BI-positive AFs (France n = 49; overseas n = 14) could be genotyped based on an analysis of eight nucleotide polymorphisms (SNPs) located within the B1 gene. Following high-resolution melting (HRM) analysis, minisequencing was carried out for each of the eight SNPs. DNA from six reference strains was included in the study, and AFs were assigned to one of the three major lineages (Types I, II, and III). In total, 26 genotypes were observed, and the hierarchical clustering distinguished two clades in lineages II (IIa, n = 30 and IIb, n = 4) and III (IIIa n = 23 and IIIb n = 6). There was an overrepresentation of overseas isolates in Clade IIb (4/4, 100%) and Clade IIIa (8/22; 36.4%) (p <0.0001), whereas medical interruption and fetal death were overrepresented in Clade IIb (2/4, 50%) and Clade IIIa (4/23, 17.4%) (p = 0.049). Conclusions Although the current genotyping system cannot pretend to replace multilocus typing, we clearly show that targeting the multicopy B1 gene yields a genotyping capacity of AFs around 20% better than when single copy targets are used. The

  1. Single Nucleotide Polymorphism Microarray Analysis in Cortisol-Secreting Adrenocortical Adenomas Identifies New Candidate Genes and Pathways1 2

    PubMed Central

    Ronchi, Cristina L; Leich, Ellen; Sbiera, Silviu; Weismann, Dirk; Rosenwald, Andreas; Allolio, Bruno; Fassnacht, Martin

    2012-01-01

    The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix SNP 6.0) to detect copy number alterations (CNAs) and copy-neutral losses of heterozygosity (cnLOH) in 15 cortisol-secreting adrenocortical adenomas with matched blood samples. We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion. We identified 962 CNAs with a median of 18 CNAs per sample. Half of them involved noncoding regions, 89% were less than 100 kb, and 28% were found in at least two samples. The most frequently gained regions were 5p15.33, 6q16.1, 7p22.3-22.2, 8q24.3, 9q34.2-34.3, 11p15.5, 11q11, 12q12, 16q24.3, 20p11.1-20q21.11, and Xq28 (≥20% of cases), most of them being identified in the same three adenomas. These regions contained among others genes like NOTCH1, CYP11B2, HRAS, and IGF2. Recurrent losses were less common and smaller than gains, being mostly localized at 1p, 6q, and 11q. Pathway analysis revealed that Notch signaling was the most frequently altered. We identified 46 recurrent CNAs that each affected a single gene (31 gains and 15 losses), including genes involved in steroidogenesis (CYP11B1) or tumorigenesis (CTNNB1, EPHA7, SGK1, STIL, FHIT). Finally, 20 small cnLOH in four cases affecting 15 known genes were found. Our findings provide the first high-resolution genome-wide view of chromosomal changes in cortisol-secreting adenomas and identify novel candidate genes, such as HRAS, EPHA7, and SGK1. Furthermore, they implicate that the Notch1 signaling pathway might be involved in the molecular pathogenesis of adrenocortical tumors. PMID:22496620

  2. Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ2 gene on metabolic syndrome risk: a meta-analysis.

    PubMed

    Zhang, Ruyi; Wang, Jiao; Yang, Rui; Sun, Jia; Chen, Rongping; Luo, Haizhao; Liu, Duan; Cai, Dehong

    2014-02-01

    Associations between peroxisome proliferator-activated receptor γ2 (PPARγ2) gene polymorphism and metabolic syndrome risk remained controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between Pro12Ala polymorphism in PPARγ2 gene and metabolic syndrome susceptibility. An electronic literature search was conducted on Medline, OVID, Cochrane Library database, and the China National Knowledge Internet up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the fixed or random effects model. Ten studies involving a total of 4456 cases and 10343 controls were included in this meta-analysis. No statistical evidence of association was found between Pro12Ala polymorphism and metabolic syndrome risk in all genetic models (homozygote model: OR=0.83, 95% CI=0.62-1.12; heterozygote model: OR=1.04, 95% CI=0.94-1.14; dominant model: OR=1.02, 95% CI=0.93-1.12; recessive model: OR=0.83, 95% CI=0.62-1.11). No statistical evidence of significant association was observed when stratified by ethnicity, definition of metabolic syndrome, source of control groups and quality score of the selected articles. All in all, the results did not support a major role of the Pro12Ala variant of the PPARγ2 gene in metabolic syndrome risk. This meta-analysis suggested that the effect of Pro12Ala polymorphism in PPARγ2 gene may not be related to metabolic syndrome as an entity. However, Pro12Ala may affect the single component of metabolic syndrome. A large, well designed study is required to more adequately assess the role for Pro12Ala polymorphism on metabolic syndrome. © 2013 Elsevier B.V. All rights reserved.

  3. Common polymorphisms in CD44 gene and susceptibility to cancer: a systematic review and meta-analysis of 45 studies

    PubMed Central

    Fang, Tingting; Cai, Yangke; Xu, Yue; Yan, Cunye; Zhang, Li; Liang, Chaozhao

    2016-01-01

    CD44 is one of the commonly recognized stem cell markers, which plays a critical role in many cancer related cellular processes. Relationships between CD44 polymorphisms and cancer risk have been widely investigated previously, whereas results derived from these studies were inconclusive and controversial. We conducted present meta-analysis aiming to explore the association between CD44 polymorphisms and cancer risk. We calculated pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) to make the evaluation clear. Embase, Web of Science, PubMed and Cochrane Library databases were retrieved to identify all eligible publications. As a result, a total of 12 publications comprised 25,777 cases and 27,485 controls fulfilled the inclusion criteria. Nevertheless, the pooled analyses suggested that no significant association was uncovered between CD44 (rs10836347, rs11821102, rs13347, rs1425802, rs353639, rs713330 and rs187115) polymorphisms with overall cancer risk. Subsequently, we conducted subgroup analysis for rs13347 polymorphism based on source of control, and we identified a significantly increased cancer risk for the population-based (P-B) group restricted to a recessive model (TT vs. TC+CC: OR = 2.030, 95%CI: 1.163-3.545, PAdjust < 0.001). In conclusion, our meta-analysis demonstrates that CD44 polymorphisms may not represent risk factors for cancer. Future well-designed large-scale case-control studies are warranted to verify our findings. PMID:27738347

  4. Correlation analysis between ApoM gene-promoter polymorphisms and coronary heart disease

    PubMed Central

    Zhang, Yao; Huang, Li-Zhu; Liu, Yan; Yang, Qing-Ling; Zhou, Xin

    2016-01-01

    Summary Objectives: Apolipoprotein M (ApoM), a 25-kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with high-density lipoprotein cholesterol (HDL-C). Studies have suggested ApoM to be important for the formation of pre-β-HDL and to increase cholesterol efflux from macrophage foam cells. The aim of this study was to explore the association of single-nucleotide polymorphisms(SNPs) in the ApoM promoter with coronary atherosclerotic disease (CAD), and the contribution of latent factors. Methods: ApoM was measured in samples from two separate case–control studies, of whom 88 patients developed CAD and 88 were controls. Whole-blood samples from subjects were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Luciferase activities were measured for HepG2 cells with two SNPs, rs805296 (T-778C) and rs940494 (T-855C), and after interfering with or overexpressing the predicted transcription factors. The ability of the SNPs to combine with nucleoproteins was analysed by electophoretic mobility shift assay (EMSA). Results: Mean plasma ApoM concentrations in the CAD and non-CAD groups were 9.58 ± 4.30 and 12.22 ± 6.59 μg/ ml, respectively. Correlation studies of ApoM concentrations with several analytes showed a marked positive correlation with HDL-C, fasting plasma glucose and triglyceride levels. The CC genotype showed lower luciferase activities compared to the TC and TT genotypes. The ApoM-855 mutant-typecould bind to the AP-2α. Interference and overexpression of AP-2 increased and decreased luciferase activities of the wild and mutant types to different degrees. Conclusion:: ApoM may be a biomarker of CAD. ApoM- 855 T→C substitution provides binding sites for AP-2α and reduces ApoM transcription activity. PMID:27841911

  5. Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population.

    PubMed

    Boukortt, Kawther Nourelhouda; Saidi-Ouahrani, Nadjia; Boukerzaza, Boubaker; Ouhaibi-Djellouli, Hadjira; Hachmaoui, Khalida; Benaissa, Fatima Zohra; Taleb, Leila; Drabla-Ouahrani, Hayet; Deba, Tahria; Ouledhamou, Sid Ahmed; Mehtar, Nadhera; Boudjema, Abdellah

    2015-10-01

    There is strong evidence that genetic as well as environmental factors affect the development of periodontitis. Various studies suggest that genetic polymorphisms of the interleukin-1 (IL-1) genes are associated with an increased risk of developing the pathogenesis. The aim of the present study was to investigate the possible relationship between two polymorphisms of IL-1 gene cluster IL-1B (C+3954T) (rs1143634) and IL-1A (C-889T) (rs1800587) SNPs and the aggressive and chronic periodontitis risk in a case control study in Algerian population. 279 subjects were recruited and received a periodontal examination: 128 healthy controls and 151 cases. From cases, 91 patients were having a chronic disease whereas 60 subjects with aggressive form. All these subjects were genotyped for IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms using TaqMan real time PCR technology. Frequencies of IL-1 alleles, genotypes and the haplotypes were also examined. Significant differences were found in the carriage rate of both minor alleles of the IL-1A (C-889T) and IL-1B (C+3954T) polymorphisms of aggressive periodontitis cases compared with healthy controls (OR [95%CI]=1.61 [1.03-2.49], p=0.03), (OR [95%CI]=1.69 [1.09-2.63], p=0.01), respectively. The result did not reach significance with the chronic form. The studied polymorphisms of the IL-1 genes appear to be associated with susceptibility to aggressive periodontitis (AgP) in the Algerian population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Endothelial nitric oxide synthase G894T gene polymorphism and essential hypertension in the Chinese population: a meta-analysis involving 11,248 subjects.

    PubMed

    Li, Yan-yan

    2011-01-01

    The endothelial nitric oxide synthase (eNOS) G894T gene polymorphism has been suggested to be linked to the risk of essential hypertension (EH), however the results are still debatable. To assess the association between eNOS G894T gene polymorphism and EH, such electronic databases as Pubmed, Embase, Web of Science, China Biological Medicine Database (CBMD) and China National Knowledge Infrastructure (CNKI) were searched. The selection criteria were as follows: a) Evaluation of the association of eNOS G894T gene polymorphism and EH. b) EH diagnosis in compliance with EH diagnosis criteria of the World Health Organization (WHO) in 1999. c) The study results were in line with the Hardy-Weinberg equilibrium (HWE). In 23 separate studies with 11,248 subjects the relation between eNOS G894T gene polymorphism and EH was analyzed by current meta-analysis. Random effect model was used to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95% CI). In this eNOS G894T gene polymorphism and EH meta-analysis in the Chinese population, the distribution of T allele frequency was 0.154 for EH group and 0.128 for the control group. A significant association was found between G894T gene polymorphism and EH (p=0.0007). The pooled OR for the distribution frequency of T allele was 1.33 (95% CI:1.13-1.56, P(heterogeneity) <0.00001). In the stratified analysis by ethnicity, there was a significant association in Han subgroup (p=0.005). The pooled OR for the distribution frequency of T allele was 1.31 (95% CI:1.09-1.59, P(heterogeneity) <0.00001). No significant increased risk for EH was found in the non-Han subgroup (p=0.08). In the current meta-analysis, T allele of eNOS G894T gene was suggested to be related to the increased risk of EH in the Chinese population, particularly in those of Han ethnicity.

  7. Meta-analysis of polymorphism rs6311 and rs6313 in the 5-HT2AR gene and schizophrenia.

    PubMed

    Sun, Li; Xu, Ping; Zhou, Yan-Gang; Zuo, Shan-Ru; Liu, Yi-Ping

    2017-01-01

    rs6311 and rs6313 polymorphism of 5-hydroxytryptamine 2A receptor has been widely studied regarding association with susceptibility to schizophrenia, but the results remained inconsistent. This study aimed to assess the association between rs6311 and rs6313 polymorphism and schizophrenia using a meta-analysis. Pubmed, Web of Science, and Embase databases were searched for all articles linking rs6311 and rs6313 polymorphism and schizophrenia. All studies which met the inclusion and exclusion criteria were included in this meta-analysis. Pooled odds ratio and 95% confidence intervals were used to evaluate the association between rs6311 and rs6313 polymorphism and schizophrenia risk. Sub-group analysis was also performed by different ethnic studies (Asian and Caucasian) and different minor allelic studies (rs6311: minor allele = A and minor allele = G; rs6313: minor allele = T and minor allele = C). Forty articles, including 50 case-control studies, were included in this meta-analysis. Specifically, 12 studies with 4100 cases and 4541 controls involved rs6311, 38 studies with 8960 cases and 9729 controls involved rs6313. The results showed that rs6311 and rs6313 were not associated with schizophrenia. Moreover, no associations were found between rs6311 and schizophrenia in different sub-groups, rs6313 was found to associated with schizophrenia among studies in which C is the minor allele. This meta-analysis indicates that rs6311 and rs6313 polymorphisms of 5-HT2AR are not associated with schizophrenia. However, the rs6313 polymorphism is associated with schizophrenia in studies in which the minor allele is C.

  8. Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

    PubMed Central

    Tong, Yu; Lin, Ying; Zhang, Yuan; Yang, Jiyun; Zhang, Yawei; Liu, Hengchuan; Zhang, Ben

    2009-01-01

    Background Transcription factor 7-like 2 (TCF7L2) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the TCF7L2 gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action. Methods Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (OR). Publication bias and study-between heterogeneity were also examined. Results The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian OR for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (CrI): 1.790, 2.157), 1.406 (95% CrI: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%CrI: 1.698, 2.088), 1.360 (95% CrI: 1.291, 1.433), respectively. Four ORs among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (P > 0.10). Pooled ORs fit a codominant, multiplicative genetic model for all the four polymorphisms of TCF7L2 gene, and this model was also confirmed in different ethnic populations when

  9. Endothelial nitric oxide synthase gene G894T polymorphism and myocardial infarction: a meta-analysis of 34 studies involving 21,068 subjects.

    PubMed

    Luo, Jian-Quan; Wen, Jia-Gen; Zhou, Hong-Hao; Chen, Xiao-Ping; Zhang, Wei

    2014-01-01

    Researches have revealed that the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting. A meta-analysis was conducted to investigate the association between eNOS G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between eNOS G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model. A total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The eNOS G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08-1.84; P = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06-1.70; P = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04-1.34; P = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between eNOS G894T polymorphism and MI risk among non-Asians (P>0.05), but a positive significant association was found among Asians (P<0.05). The eNOS G894T polymorphism is associated with increased MI risk in Asians. The results indicate that ethnicity plays important roles in the association between eNOS G894T polymorphism and MI.

  10. Relationships of common polymorphisms in IL-6, IL-1A, and IL-1B genes with susceptibility to osteoarthritis: a meta-analysis.

    PubMed

    Cai, Hao; Sun, Huan-Jian; Wang, You-Hua; Zhang, Zhe

    2015-08-01

    Observational and experimental studies have arrived at inconsistent conclusions about whether common polymorphisms in IL-6, IL-1A, and IL-1B genes are associated with an increased risk of osteoarthritis (OA). Therefore, we undertook a comprehensive meta-analysis to more systematically summarize the relationships of IL-6, IL-1A, and IL-1B genetic polymorphisms with susceptibility to OA. We screened the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases up to 31 March 2014. We used STATA software to analyze statistical data. Odds ratios (ORs) and their corresponding 95 % confidence intervals (95 % CIs) were calculated. Seventeen independent case-control studies were included in this meta-analysis with a total number of 7,491 subjects, comprised of 3,293 OA patients and 4,729 healthy controls. Our results indicate that IL-6, IL-1A, and IL-1B genetic polymorphisms are statistically correlated with an increased risk of OA under the allele and dominant models. According to a subgroup analysis based on disease, a higher frequency of IL-6 genetic polymorphisms was observed among knee OA and hand OA patients, but not among hip OA and DIP OA patients. A higher frequency of IL-1A genetic polymorphisms were found among hip OA patients, hand OA, hip OA and DIP OA patients. Furthermore, we observed a higher IL-1B polymorphism frequency among knee OA and hip OA patients, but not among hand OA patients. Our findings provide evidence that IL-6, IL-1A, and IL-1B genetic polymorphisms may be correlated with susceptibility to OA.

  11. Single-strand conformation polymorphism analysis of candidate genes for reliable identification of alleles by capillary array electrophoresis.

    PubMed

    Kuhn, David N; Borrone, James; Meerow, Alan W; Motamayor, Juan C; Brown, J Steven; Schnell, Raymond J

    2005-01-01

    We investigated the reliability of capillary array electrophoresis-single strand conformation polymorphism (CAE-SSCP) to determine if it can be used to identify novel alleles of candidate genes in a germplasm collection. Both strands of three different size fragments (160, 245 and 437 bp) that differed by one or more nucleotides in sequence were analyzed at four different temperatures (18 degrees C, 25 degrees C, 30 degrees C, and 35 degrees C). Mixtures of amplified fragments of either the intron interrupting the C-terminal WRKY domain of the Tc10 locus or the NBS domain of the TcRGH1 locus of Theobroma cacao were electroinjected into all 16 capillaries of an ABI 3100 Genetic Analyzer and analyzed three times at each temperature. Multiplexing of samples of different size range is possible, as intermediate and large fragments were analyzed simultaneously in these experiments. A statistical analysis of the means of the fragment mobilities demonstrated that single-stranded conformers of the fragments could be reliably identified by their mobility at all temperatures and size classes. The order of elution of fragments was not consistent over strands or temperatures for the intermediate and large fragments. If samples are only run once at a single temperature, small fragments could be identified from a single strand at a single temperature. A combination of data from both strands of a single run was needed to identify correctly all four of the intermediate fragments and no combination of data from strands or temperatures would allow the correct identification of two large fragments that differed by only a single single-nucleotide polymorphism (SNP) from a single run. Thus, to adequately assess alleles at a candidate gene locus using SSCP on a capillary array, fragments should be < or =250 bp, samples should be analyzed at two different temperatures between 18 degrees C and 30 degrees C to reduce the variability introduced by the capillaries, data should be combined

  12. Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis.

    PubMed

    Żur-Wyrozumska, Kamila; Pera, Joanna; Dziubek, Anna; Sado, Małgorzata; Golenia, Aleksandra; Słowik, Agnieszka; Dziedzic, Tomasz

    Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population. We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System. The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population. Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Single nucleotide polymorphism in the SEPS1 gene may contribute to the risk of various human diseases: a meta-analysis.

    PubMed

    Sun, Hong-Yun; Liu, Tai-Bin; Wang, Qing-Chang; Wu, Wei-Qiang; He, Yu-Jing

    2016-09-01

    Recently the G-105A promoter polymorphism in SEPS1 has been shown to increase pro-inflammatory cytokine expression and, thus, to be correlated with various types of human cancers and diseases. This study examined whether this functional polymorphism was related to the risks of several human diseases by performing a meta-analysis. This study identified all published studies in MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, Current Contents Index and three Chinese databases. Eleven case-control studies were incorporated into this meta-analysis. The results showed that carriers of the rs28665122 G > A polymorphism in the SEPS1 gene are at increased risk of developing diseases under five genetic models. According to the ethnicity-stratified sub-group analysis, SEPS1 rs28665122 polymorphism is significantly linked to increased risk of developing related diseases in Europeans under five genetic models; but not among Asians. This data indicates a statistical association between SEPS1 rs28665122 G > A variants and the development of various human diseases. Such findings suggest that SEPS1 may be a potential gene marker for disease diagnosis and prognosis.

  14. An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma.

    PubMed

    Yao, Ying-Shui; Chang, Wei-Wei; He, Lian-Ping; Jin, Yue-Long; Li, Chao-Pin

    2016-12-01

    The association between TGF-β1 polymorphisms and asthma risk has been widely reported, but results were controversial. We performed this meta-analysis based on the Preferred Reporting Items for Systematic Reviews and meta-analyses statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI were searched for eligible articles published up to September, 2013. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a total of 20 articles were identified, 17 studies with 3694 cases and 5613 controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C polymorphism. For C-509T, significant associations with asthma were found in Asians (TT+TC vs. CC: P=0.004, OR=1.43, 95%CI=1.12-1.81, Pheterogeneity=0.001) and in Caucasians (P=0.05, OR=1.16, 95%CI=1.00-1.34, Pheterogeneity=0.36). With respect to T869C, a small significant association was observed in overall analysis of allele contrasts(C vs. T: OR=1.14, 95%CI: 1.01-1.29, P=0.03) and homozygote comparison (CC vs. TT: OR=1.29, 95%CI: 1.00-1.65, P=0.05), but no significant risks were found among Caucasian population and Asian population. For G915C polymorphism, no significant association with asthma risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Association analysis of endothelial nitric oxide synthase G894T gene polymorphism and erectile dysfunction complaints in a population-based survey.

    PubMed

    Andersen, Monica L; Guindalini, Camila; Santos-Silva, Rogerio; Bittencourt, Lia Rita A; Tufik, Sergio

    2010-03-01

    Erectile dysfunction (ED) is a common disorder leading to a serious, negative impact on the quality of the patient's life. The gene encoding endothelial nitric oxide synthase (eNOS) is an interesting candidate gene for understanding the physiopathology of ED, as it is involved in the catalytic production of nitric oxide (NO), the neurotransmitter that plays a critical role in penile tumescence and erection. To evaluate a potential association between the G894T polymorphism in the eNOS gene and ED complaints in a population-based sample in São Paulo, Brazil. The prevalence of ED complaints was estimated according to the answer to the question "How would you describe your ability to get and keep an erection that is adequate for satisfactory intercourse?" ED was considered to be present if the response was "sometimes" or "never." A total of 449 men were enrolled in the study and answered an eight-item questionnaire to ascertain sexual performance/ED and satisfaction. The eNOS G894T polymorphism was genotyped using a standard polymerase chain reaction method. Univariate analysis demonstrated that ED was associated with diabetes, hypertension, sleep apnea severity, increasing age and body mass index, as well as testosterone levels (P < 0.05). Forward multiple regression models indicated that age was the only independent factor associated with ED in this population (odds ratio = 1.09; 95% CI 1.06-1.11; P < 0.0001). Genotypic and allelic analyses provided no evidence for an association between this polymorphism and the risk for ED complaints in this sample. Population stratification did not affect the association test results. This is the first study to examine the effect of polymorphisms in the eNOS gene and the risk for ED utilizing a case-control approach in the Brazilian population. Our results do not support a major role for eNOS gene polymorphisms in ED in this population.

  16. Smoking and selected DNA repair gene polymorphisms in controls: Systematic review and meta-analysis

    PubMed Central

    Hodgson, M. Elizabeth; Poole, Charles; Olshan, Andrew F.; North, Kari E.; Zeng, Donglin; Millikan, Robert C.

    2010-01-01

    Background When the case-only study design is used to estimate statistical interaction between genetic (G) and environmental (E) exposures, G and E must be independent in the underlying population, or the case-only estimate of interaction (COR) will be biased. Few studies have examined the occurrence of G-E association in published control group data. Methods To examine the assumption of G-E independence in empirical data, we conducted a systematic review and meta-analysis of G-E associations in controls for frequently investigated DNA repair genes (XRCC1 Arg399Gln, Arg194Trp, or Arg280His, XPD Lys751Gln, and Asp312Asn, and XRCC3 Thr241Met) and smoking (ever/never smoking, current/not current smoker, smoking duration, smoking intensity and pack-years). Results Across the 55 included studies, SNP-smoking associations in controls (ORz) were not reliably at the null value of 1.0 for any SNP-smoking combinations. Two G-E combinations were too heterogeneous for summary estimates: XRCC1 399 and ever-never smoking (N=21), and XPD 751 and pack-years (N=12). ORz ranges for these combinations were: [ORz (95% confidence interval (CI)] 0.7 (0.4, 1.2) – 1.9 (1.2, 2.8) and 0.8 (0.5, 1.3) – 2.3 (0.8, 6.1), respectively). Estimates for studies considered homogeneous (Cochran’s Q p-value <0.10) varied 2- to 5-fold. No study characteristics were identified that could explain heterogeneity. Conclusions We recommend the independence assumption be evaluated in the population underlying any potential case-only study, rather than in a proxy control group(s) or pooled controls. Impact These results suggest that G-E association in controls may be population-specific. Increased access to control data would improve evaluation of the independence assumption. PMID:20935063

  17. Analysis of Fcgrt gene polymorphism in indigenous Chinese sheep and its association with colostrum IgG concentration.

    PubMed

    Tian, Z H; Shi, F; Zhong, F G; Bai, D P; Zhang, X Y

    2015-03-30

    The neonatal Fc receptor (FcRn) plays an important role in regulating IgG homeostasis in the body and passive protection to the offspring. Changes in FcRn expression levels caused by genetic polymorphisms of Fcgrt, which encodes FcRn, may lead to inter-individual differences in colostrum IgG levels in sheep. In this study, we sequenced the FcRn partial heavy chain from 179 sheep from Xinjiang Province, China, and detected the differences in colostrum IgG levels and Fcgrt genotypes to identify the correlation between the Fcgrt genotype and colostrum IgG levels in 4 sheep breeds. The DNA sequencing of a 680-bp fragment of the Fcgrt gene revealed various patterns depending on the single-strand conformation in the Suffolk breed. Sequencing analysis revealed a total of 3 patterns, AA, BB, AB, in this fragment, among which the absence of AB and BB genotype acted as a marker for breed identification and characterization, while the AA genotype was shared by Suffolk and 3 other breeds. The only allele found in all 4 breeds was allele A, indicating that natural selection may be favoring the AB and BB genotypes in general and B allele in particular, as the colostrum IgG concentration was relatively higher in the Suffolk breed compared to the other 3 breeds.

  18. Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients

    SciTech Connect

    Shaikh, S.; Collier, D.A.; Sham, P.

    1995-12-18

    We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine`s action being at D4 receptors. 28 refs., 1 fig., 3 tabs.

  19. Genetic association between the cyclin-dependent kinase inhibitor gene p27/Kip1 polymorphism (rs34330) and cancer susceptibility: a meta-analysis

    PubMed Central

    Cheng, Xiao-Ke; Wang, Xue-Jun; Li, Xiao-Dong; Ren, Xue-Qun

    2017-01-01

    The p27 rs34330 (-79C/T) polymorphism has been widely studied for human cancer susceptibility. The current findings, however, still remained controversial. Therefore, we performed the meta-analysis to provide a more accurate result. Eligible studies were identified from PubMed database up to June 2015. The association of p27 rs34330 polymorphism and cancer susceptibility was estimated with odds ratios and corresponding 95% confidence intervals. The meta-analysis was performed with Stata 12. A total of ten studies with 11,214 cases and more than 8,776 controls were included in the meta-analysis (including breast, lung, thyroid, endometrial, and hepatocellular cancer). In pooled analysis, p27 gene rs34330 polymorphism significantly increased the cancer susceptibility. Subgroup analysis indicated that the elevated risk was observed under all the genetic models for Asians and under three genetic models for Caucasians. Results of sensitivity analysis were similar to the overall results. The results suggested that the p27 rs34330 polymorphism increased the cancer susceptibility, especially in Asians. Further well-designed and large sample size studies are warranted to verify the conclusion. PMID:28317869

  20. Analysis of BIM (BCL-2 like 11 gene) deletion polymorphism in Chinese non-small cell lung cancer patients.

    PubMed

    Zhong, Jia; Li, Zheng-Xiang; Zhao, Jun; Duan, Jian-Chun; Bai, Hua; An, Tong-Tong; Yang, Xiao-Dan; Wang, Jie

    2014-11-01

    Drug resistance significantly weakens the efficacy of cancer treatment, and the BIM (also known as the BCL2L11 gene) deletion polymorphism has been identified as a potential biomarker for drug resistance. In this retrospective study, we included a total of 290 patients with advanced non-small cell lung cancer (NSCLC) who received treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy. The BIM deletion polymorphism of each patient was detected by polymerase chain reaction. EGFR mutations were detected by denaturing high-performance liquid chromatography methods and the amplification refractory mutation system. The BIM deletion polymorphism was detected in 45/290 (15.5%) Chinese NSCLC patients. No associations were observed between the BIM deletion and clinic-pathologic characteristics of patients. The BIM deletion polymorphism was predictive of shorter progression-free survival in Chinese patients with EGFR-mutant adenocarcinoma and who were treated with EGFR-TKIs (7.30 vs. 9.53 months, P = 0.034). Additionally, we found that the BIM deletion polymorphism was an effective predictor of short progression-free survival in individuals with EGFR-mutant NSCLC and treated with chemotherapy containing pemetrexed (3.32 vs. 5.30, P = 0.012) or second-/beyond-line chemotherapy containing taxanes (1.53 vs. 2.61 months, P = 0.025). The BIM deletion was not correlated with overall survival. The BIM deletion polymorphism occurs in 15.5% of Chinese NSCLC patients, and is a biomarker for resistance to TKIs and chemotherapy. However, BIM deletion was not a decisive factor in overall survival.

  1. Analysis of the porcine APOA2 gene expression in liver, polymorphism identification and association with fatty acid composition traits.

    PubMed

    Ballester, M; Revilla, M; Puig-Oliveras, A; Marchesi, J A P; Castelló, A; Corominas, J; Fernández, A I; Folch, J M

    2016-10-01

    APOA2 is a protein implicated in triglyceride, fatty acid and glucose metabolism. In pigs, the APOA2 gene is located on pig chromosome 4 (SSC4) in a QTL region affecting fatty acid composition, fatness and growth traits. In this study, we evaluated APOA2 as a candidate gene for meat quality traits in an Iberian × Landrace backcross population. The APOA2:c.131T>A polymorphism, located in exon 3 of APOA2 and determining a missense mutation, was associated with the percentage of hexadecenoic acid [C16:1(n-9)], linoleic acid [C18:2(n-6)], α-linolenic acid [C18:3(n-3)], dihomo-gamma-linolenic acid [C20:3(n-6)] and polyunsaturated fatty acids (PUFAs) in backfat. Furthermore, this SNP was associated with the global mRNA expression levels of APOA2 in liver and was used as a marker to determine allelic expression imbalance by pyrosequencing. We determined an overexpression of the T allele in heterozygous samples with a mean ratio of 2.8 (T/A), observing a high variability in the allelic expression among individuals. This result suggests that complex regulatory mechanisms, beyond a single polymorphism (e.g. epigenetic effects or multiple cis-acting polymorphisms), may be regulating APOA2 gene expression. © 2016 Stichting International Foundation for Animal Genetics.

  2. MTHFR gene A1298C polymorphisms are associated with breast cancer risk among Chinese population: evidence based on an updated cumulative meta-analysis.

    PubMed

    Wang, Yadong; Yang, Haiyan; Duan, Guangcai

    2015-01-01

    Published studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphisms and breast cancer risk among Chinese population have yielded conflicting results. The purpose of this study was to clarify the association between MTHFR gene A1298C polymorphisms and breast cancer risk among Chinese population. Systematic searches were performed through the database of Medline/PubMed, Science Direct, Elsevier, CNKI and Wanfang Medical Online. Overall, a significantly increased risk of breast cancer was observed among the subjects carrying MTHFR gene A1298C AC+CC genotype (odds ratio [OR]=1.05 with 95% confidence interval [CI]: 1.01-1.10) as compared to those carrying AA genotype among total Chinese population. We did not observe any significant association between MTHFR gene A1298C polymorphisms and the risk of breast cancer under the additional genetic models of AC vs. AA, CC vs. AA and C-allele vs. A-allele (OR=1.00 with 95% CI: 0.97-1.02, OR=1.01 with 95% CI: 1.00-1.02 and OR=1.00 with 95% CI: 0.99-1.02, respectively). The cumulative meta-analysis showed similar results. In subgroup analysis, we observed subjects carrying AC+CC genotype had an increased breast cancer risk compared with those carrying AA genotype among the studies of sample size less than 1000. We did not observe any significant association between MTHFR gene A1298C polymorphisms and breast cancer risk in additional subgroup analyses. Our results suggest that MTHFR gene A1298C AC+CC genotype may be a risk factor for the development of breast cancer among Chinese population. Well-designed studies with a large sample size are needed to further confirm our findings.

  3. A meta-analysis of association between glutathione S-transferase M1 gene polymorphism and Parkinson’s disease susceptibility

    PubMed Central

    Weikang, Chen; Likang, Lan; Weiwen, Qiu; Liping, Lu

    2016-01-01

    Abstract The aim of this meta-analysis was to evaluate whether there was an association between glutathione S-transferase M1(GSTM1)gene polymorphism and Parkinson’s disease (PD) susceptibility by pooling published data. We performed comprehensive electronic database search for articles published between February12,2015 and April30 2016. The published case-control or cohort studies related to GSTM1 gene polymorphism and Parkinson’s disease susceptibility were screened, reviewed, and included in this meta-analysis. The correlation between GSTM1 gene polymorphism and PD susceptibility was expressed by odds ratio (OR) and its corresponding 95% confidence interval (95%CI). Publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test. All analysis was done by stata11.0 software. After searching the PubMed, EMBASE, and CNKI databases, seventeen case-control studies with 3,538 PD and 5,180 controls were included in the final meta-analysis. The data was pooled by a fixed-effect model for lack of statistical heterogeneity across the studies; the results showed GSTM1 null expression can significant increase the susceptibility of PD (OR=1.11, 95% CI:1.01-1.21, P<0.05). Subgroup analysis indicated GSTM1 gene polymorphism was associated with PD susceptibility in the Caucasian ethnic group (OR=1.15, 95% CI:1.05-1.27, P<0.05) but not in the Asian ethnic group (OR=0.89, 95% CI:0.70-1.12, P>0.05). Begg’s funnel plot and Egger’s line regression test showed no significant publication bias. Based on the present evidence, GSTM1 null expression can significant increase the susceptibility of PD in persons of Caucasian ethnicity. PMID:28352849

  4. Relationship between Interleukin-6 (−174G/C and −572C/G) Promoter Gene Polymorphisms and Risk of Intracerebral Hemorrhage: A Meta-Analysis

    PubMed Central

    Kumar, Pradeep; Misra, Shubham; Kumar Yadav, Arun; Kumar, Amit; Sriwastva, Mukesh; Prasad, Kameshwar

    2016-01-01

    Background Polymorphisms of −174G/C and −572C/G in the Interleukin-6 (IL-6) promoter gene can affect both transcription and secretion of IL-6 and may be involved in the inflammatory mechanisms in early and delayed phases after intracerebral hemorrhage (ICH). The role of these polymorphisms remains unclear for the pathogenesis of ICH. Methods PubMed, EMBASE, MEDLINE and Google Scholar searches were conducted from January 1, 1950 to February 29, 2016 and were supplemented with relevant articles identified in the references. The following search terms were used: (‘interleukin-6’ or ‘IL-6’) and (‘genetic polymorphism’ or ‘single nucleotide polymorphisms’ or ‘SNP’) and (‘intracerebral hemorrhage’ or ‘ICH’) and (‘hemorrhagic stroke’ or ‘HS’). Fixed or random effects models were used to estimate the pooled odds ratios and 95% confidence intervals. Begg's funnel plot was used to assess the potential for publication bias. Results In our meta-analysis, three case-control studies involving 446 ICH cases and 2,322 controls were included. No significant association was observed for the IL-6 (-174G/C and −572C/G) gene polymorphisms with the risk of ICH under dominant, recessive and allelic models. Conclusion Our meta-analysis suggests that IL-6 gene polymorphisms are not associated with the risk of ICH. However, caution must be taken while considering the results of our meta-analysis due to the presence of small sample size. Our results cannot be extrapolated to represent the effect of entire IL-6 genetic polymorphism on stroke patients worldwide. Therefore, further well-designed studies with large sample size are warranted to validate our findings and provide a profound conclusion. PMID:27752477

  5. Phylogenetic analysis of Rutaceous plants based on single nucleotide polymorphism in chloroplast and nuclear gene sequences

    USDA-ARS?s Scientific Manuscript database

    The family Rutaceae encompasses several genera including the economically important genus Citrus. In this study, we selected 22 citrus relatives belonging to the various sub groups of Rutaceae and compared the sequences of three gene fragments. The accessions selected belong to the subfamily Rutoide...

  6. Association of endothelia nitric oxide synthase gene rs1799983 polymorphism with susceptibility to prostate cancer: a meta-analysis.

    PubMed

    Wu, Jian Hui; Yang, Kuo; Ma, Hong Shun; Xu, Yong

    2014-07-01

    Genetic polymorphism of endothelial nitric oxide synthase (NOS3) rs1799983 (Glu298Asp) has been implicated to alter the risk of prostate cancer, but the results are controversial. Two investigators independently searched the PubMed, Cochrane Library, and Embase electronic databases up to September 30, 2013. Summary odds ratios (OR) and 95 % confidence interval (CI) for rs1799983 polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 11.0. A total of 7 independent studies, including 1,792 cases and 2,411 controls, were identified. Our analysis suggested that rs1799983 was associated with prostate cancer risk in overall population under dominant model (OR = 1.15, 95%CI = 1.01-1.30, P = 0.03) and allelic model (OR = 1.11, 95%CI = 1.00-1.22, P = 0.04). In the subgroup analysis, we detected no association between rs1799983 polymorphism and prostate risk in Caucasian population under all the genetic models. This meta-analysis showed the evidence that NOS3 rs1799983 polymorphism was associated with a risk of prostate cancer development in overall populations.

  7. MULTIPLE ENZYME RESTRICTION FRAGMENT LENGTH POLYMORPHISM ANALYSIS FOR HIGH RESOLUTION DISTINCTION OF PSEUDOMONAS (SENSU STRICTO) 16S RRNA GENES

    EPA Science Inventory

    Pseudomonas specific 16S rDNA PCR amplification and multiple enzyme restriction fragment length polymorphism (MERFLP) analysis using a single digestion mixture of Alu I, Hinf I, Rsa I, and Tru 9I distinguished 150 published sequences and reference strains of authentic Pseudomonas...

  8. MULTIPLE ENZYME RESTRICTION FRAGMENT LENGTH POLYMORPHISM ANALYSIS FOR HIGH RESOLUTION DISTINCTION OF PSEUDOMONAS (SENSU STRICTO) 16S RRNA GENES

    EPA Science Inventory

    Pseudomonas specific 16S rDNA PCR amplification and multiple enzyme restriction fragment length polymorphism (MERFLP) analysis using a single digestion mixture of Alu I, Hinf I, Rsa I, and Tru 9I distinguished 150 published sequences and reference strains of authentic Pseudomonas...

  9. Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population

    PubMed Central

    Spire-Vayron de la Moureyre, Catherine; Debuysere, Hervé; Mastain, Bruno; Vinner, Elizabeth; Marez, Delphine; Lo Guidice, Jean-Marc; Chevalier, Dany; Brique, Serge; Motte, Kokou; Colombel, Jean-Frédéric; Turck, Dominique; Noel, Christian; Flipo, René-Marc; Pol, Annie; Lhermitte, Michel; Lafitte, Jean-Jacques; Libersa, Christian; Broly, Franck

    1998-01-01

    Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs.We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR–SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3′-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively.Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17–18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer.The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping. PMID:9831928

  10. Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population

    PubMed Central

    Li, Hua; Guo, Mingzhen; Liu, Shiguo; Li, Changgui

    2016-01-01

    Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation. PMID:26890073

  11. Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population.

    PubMed

    Zhou, Zheng; Li, Xinde; Li, Hua; Guo, Mingzhen; Liu, Shiguo; Li, Changgui

    2016-01-01

    Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.

  12. Correlation analysis between starch properties and single nucleotide polymorphisms of waxy genes in common rye (Secale cereale L.).

    PubMed

    Meng, M; Gao, X; Han, L J; Li, X Y; Wu, D; Li, H Z; Chen, Q J

    2014-01-14

    To understand the relationships between single nucleotide polymorphisms (SNPs) in the waxy gene and starch parameters in common rye, we performed sequence characterization, enzyme activity testing, amylopectin/amylose ratio evaluation, starch property testing, and correlation analysis. Specific primers were used to clone waxy from 20 rye cultivars. Sequence analysis showed that waxy was 2852 bp, including 11 exons, and sequence similarity across the 20 cultivars was over 98%. The Waxy protein showed >95% similarity with those from wheat, rice, and barley, the closest genetic relationship being with wheat Wx-A type. Waxy had multiple SNPs, most of which were located in the exons. Amino acid variants were found to be mainly distributed in the catalytic domain in an imbalanced state. Multi-factor correlation analysis revealed significant correlation among starch pasting parameters in rye flour. The Waxy protein activity was significantly negatively correlated with the amylose content and amylopectin/amylose ratio. However, pasting parameters, Waxy enzyme activity, and amylopectin/amylose content ratio were not correlated. The correlation of SNPs, the key catalytic site of Waxy, with starch parameters and enzyme activity suggested that both starch pasting parameters and Waxy protein activity were influenced by No. 260 amino acid (aa). Further, the 141 and 152 aa loci were found in the enzyme-catalyzing domain of Waxy. Interestingly, Waxy enzyme activity was also influenced by the 363 aa locus in the pliable region. These results provide important theoretical regarding the high-throughput quality identification of noodle starch, functional studies, directional selection, and molecular markers of wheat Wx subunits.

  13. Analysis of single nucleotide polymorphisms and haplotypes in the neuropeptide Y gene: no evidence for association with alcoholism in a German population sample.

    PubMed

    Zill, Peter; Preuss, Ulrich W; Koller, Gabrielle; Bondy, Brigitta; Soyka, Michael

    2008-03-01

    Several lines of evidence from animal and electrophysiological studies indicate that the neuropeptide Y (NPY) gene is involved in the pathophysiology of alcohol dependence. Recent studies have provided evidence for an association between a Leu7Pro polymorphism, as well as 2 promoter single nucleotide polymorphisms (SNPs) in the NPY gene (G-602T, T-399C) and alcohol dependence. The aim of the present study was to analyze these variants in a large sample of the Munich Gene Bank of Alcoholism. We performed single SNP and haplotype studies in 465 alcohol dependent patients and 448 healthy controls with 3 SNPs in the promoter region (-883ins/del, G-602T, T-399C) and the Leu7Pro polymorphism in exon 2 of the NPY gene. Neither single SNP-, nor haplotype analysis could detect significant associations with alcohol dependence. Additionally we could not detect any relation to Cloninger's Type 1/2 or Babor's Type A/B classification, to withdrawal symptoms, to the age of onset or to the amount of alcohol intake. In conclusion, our results suggest that the analyzed SNPs, as well as the corresponding haplotypes of the NPY gene are unlikely to play a major role in the pathophysiology of alcohol dependence in the investigated sample from the German population. Further analyses are needed to confirm the present results.

  14. Association between polymorphisms in XRCC1 gene and clinical outcomes of patients with lung cancer: a meta-analysis.

    PubMed

    Cui, Zhigang; Yin, Zhihua; Li, Xuelian; Wu, Wei; Guan, Peng; Zhou, Baosen

    2012-02-17

    X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of XRCC1 are suspected to have some relationship with response to chemotherapy and overall survival of lung cancer. This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients. We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected using specific inclusion and exclusion criteria. Primary outcomes included objective response (i.e., complete response + partial response vs. progressive disease + stable disease) and overall survival (OS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software. Twenty-two articles were included in the present analysis. XRCC1 Arg194Trp and Arg399Gln polymorphisms were significantly associated with response to treatment in lung cancer patients. Patients with C/T genotype, T/T genotype and minor variant T allele at Arg194Trp were more likely to respond to platinum-based chemotherapy compared with those with C/C genotype (C/T vs. C/C: OR, 2.54; 95%CI, 1.95-3.31; T/T vs. C/C: OR, 2.06; 95%CI, 1.39-3.06; C/T+T/T vs. C/C: OR, 2.42; 95% CI, 1.88-3.10). For XRCC1 Arg399Gln, G/A genotype, A/A genotype and minor variant A allele were associated with objective response in all patients (G/A vs. G/G: OR, 0.67; 95%CI, 0.50-0.90; A/A vs. G/G: OR, 0.43; 95%CI, 0.25-0.73; A/A+G/A vs. G/G: OR, 0.63; 95%CI, 0.49-0.83). Both G/A and A/A genotypes of XRCC1 Arg399Gln could influence overall survival of lung cancer patients (G/A vs. G/G: HR, 1.23; 95%CI, 1.06-1.44; A/A vs. G/G: HR, 2.03; 95%CI, 1.20-3.45). Interaction analysis suggested that compared with the patients carrying C

  15. Estrogen receptor α gene polymorphisms and risk of Alzheimer’s disease: evidence from a meta-analysis

    PubMed Central

    Cheng, Daye; Liang, Bin; Hao, Yiwen; Zhou, Wenling

    2014-01-01

    Objective Human estrogen receptor α (ESR1), a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) – are possibly associated with Alzheimer’s disease (AD). However, individual study results are still controversial. Materials and methods We searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD. Results The results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P=0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05). Conclusion Based on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger studies. PMID:25061285

  16. COL1A1 gene -1997G/T polymorphism and risk of osteoporosis in postmenopausal women: a meta-analysis.

    PubMed

    Yu, K H; Tang, J; Dai, C Q; Yu, Y; Hong, J J

    2015-09-21

    Studies investigating the association between the COL1A1 gene -1997G/T polymorphism and the risk of osteoporosis in postmenopausal women have reported conflicting results. We performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. We conducted searches of the published literature in the PubMed and Embase databases up to September 2014. We estimated the pooled odds ratios with their 95% confidence intervals to assess the associations using fixed- or random-effect models. Publication bias was investigated by Begg's funnel plot. Meta-analysis was performed using the STATA package version 12.0. No significant association was found between the -1997G/T polymorphism in the COL1A1 gene and osteoporosis risk in the total population analysis (TT vs GG: OR = 1.28, 95%CI = 0.76-2.17; TT vs GT: OR = 1.04, 95%CI = 0.60-1.78; dominant model: OR = 0.84, 95%CI = 0.50-1.40; recessive model: OR = 1.18, 95%CI = 0.84- 1.66). In a subgroup analysis by nationality, the results also showed that no significant associations between the COL1A1 gene -1997G/T polymorphism and osteoporosis risk existed in either Caucasian or Asian populations. No evidence of publication bias was found. In conclusion, the COL1A1 gene -1997G/T polymorphism might not be a risk factor for osteoporosis in postmenopausal women. Further large and well-designed studies are needed to confirm these conclusions.

  17. Association between aspartic acid repeat polymorphism of the asporin gene and risk of knee osteoarthritis: A systematic review and meta-analysis.

    PubMed

    Sobhan, Mohammad Reza; Mehdinejad, Masoud; Jamaladini, Mohammad Hossein; Mazaheri, Mahta; Zare-Shehneh, Masoud; Neamatzadeh, Hossein

    2017-09-07

    Studies have assessed the association between aspartic acid (D)-repeat polymorphism in the gene encoding Asporin (ASPN) and knee osteoarthritis (KOA) risk, but the results were inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between ASPN gene D-repeat polymorphism and KOA risk. Eligible studies were identified by searching several electronic databases for relevant reports published before September 2016. The pooled odds ratios (ORs) for the association between ASPN polymorphism and KOA and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed-effect model. A total of eleven case-control studies in ten publications with 4610 KOA cases and 3621 controls were included for the ASPN D-repeat polymorphism. Overall, no significant association was detected for D14 allele carrier (D14 vs. D13: OR = 1.10, 95% CI = 0.90-1.36, p = 0.32). Meta-analysis of D14 vs. other alleles and D13 vs. other alleles showed the same pattern of KOA association as the D14 vs. D13 (OR = 1.30, 95% CI = 1.00-1.70, p = 0.06; OR = 0.93, 95% CI = 0.82-1.06, p = 0.33, respectively). Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of KOA was found in the European and Asians populations (OR = 1.05, 95% CI = 0.91-1.21, p = 0.49; OR = 0.98, 95% CI = 0.78-1.23, p = 0.88, respectively). The present meta-analysis suggests that the ASPN D-repeat polymorphism is not associated with an increased KOA risk. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings. Level III diagnostic study. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  18. Five COX-2 gene polymorphisms and risk of breast cancer: an updated meta-analysis based on 19 case-control studies.

    PubMed

    Li, Qing; Liu, Liu; Liu, Yanling; Zhou, Huirong; Yang, Zhi; Yuan, Keng; Min, Weiping

    2015-01-01

    The correlationship between COX-2 gene polymorphisms and breast cancer has been wildly studied, but the results remain controversial. Hence, the present meta-analysis aimed to investigate the association between COX-2 SNPs (rs5275, rs20417, rs689466, rs5277, rs2206593) and risk of breast cancer. Data were collected from PubMed, Embase and China National Knowledge Infrastructure. Summary odds ratio (OR) with 95 % confidence interval (CI) was applied to assess the relationship. Heterogeneity test, sensitivity analysis and publication bias test were also performed. There were 17 articles that contained 19 studies in this research. Fourteen case-control studies with 15,007 breast cancer cases and 20,005 controls were concerning rs5275 polymorphism, and 8 case-control studies with 10,216 cases and 12,839 controls were about rs20417 polymorphism. Other three polymorphisms (rs689466, rs2206593, rs5277) were studied in 5, 3 and 3 studies, respectively. COX-2-rs20417 CC genotype was significantly associated with increased risk of breast cancer when comparing to G allele [ORs were 1.231 (1.050-1.444) for CC vs. GG, P = 0.01, 1.223 (1.045-1.432) for CC vs. G carrier, P = 0.01]. Furthermore, the results of the subgroup analysis by ethnicity suggested that C allele significantly contributed to the risk of breast cancer for Asians [1.459 (1.182-1.802) for GC vs. GG, 1.472 (1.201-1.805) for C carrier vs. GG]. However, no association was found for rs5275, rs689466, rs5277 and rs2206593 in all comparison modes. This meta-analysis indicated that the COX-2 rs20417 polymorphism contributed to genetic susceptibility of breast cancer. In contrast, COX-2 rs5275, rs689466, rs2206593 and rs5277 polymorphisms might be not associated with the risk of breast cancer.

  19. Association between Interleukin-6 Gene Polymorphisms and Rheumatoid Arthritis in Chinese Han Population: A Case-Control Study and A Meta-analysis

    PubMed Central

    Li, Feng; Xu, Jing; Zheng, Jiatian; Sokolove, Jeremy; Zhu, Kai; Zhang, Yuanchao; Sun, Hongsheng; Evangelou, Evangelos; Pan, Zhenglun

    2014-01-01

    The aim of this study was to investigate the possible association in the interleukin-6 (IL-6) gene with Rheumatoid arthritis (RA) in Chinese Han population from Shandong Province. Target regions of IL-6 gene were amplified by polymerase chain reaction (PCR) and genotyped. A logistic regression analysis was performed to detect potential associations in our case-control sample, the odd ratio(OR) and 95% confidence intervals(CIs) were calculated. Furthermore, we systematically tracked all the published studies in the field and performed a meta-analysis for the single nucleotide polymorphisms (SNPs) under study. 256 RA patients and 331 healthy controls were recruited into the case-control study. We found allele frequencies of rs1800795, rs1800797 and rs1474347 in RA patients differ from control subjects (P = 0.016, 0.024, 0.020, respectively). Significant difference was observed in haplotype frequencies of GCCGCT between RA patients and controls (P = 0.0001, OR = 4.066, 95%CI = 1.891 ~ 8.746), while GGCGCT frequencies was found lower in RA than controls (P = 0.006, OR = 0.669, 95%CI = 0.501 ~ 0.894). The results of the meta-analysis showed association polymorphism within the IL-6 promoter with RA. These findings suggest that rare IL-6 gene polymorphisms may associate with RA susceptibility in Han Chinese populations; however further studies are needed to assess the validity of the association of IL-6 with RA. PMID:25030201

  20. Association of XRCC3 gene rs861539 polymorphism with gastric cancer risk: evidence from a case-control study and a meta-analysis.

    PubMed

    Cheng, Shidan; Wang, Liying; Wang, Lei; Wang, Zhengting

    2015-01-01

    The association between the X-ray repair cross-complementing group 3 (XRCC3) gene Thr241Met polymorphism (rs861539) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study and the following meta analysis involving 6,520 subjects indicated null association of XRCC3 gene rs861539 polymorphism between gastric cancer patients and controls under both allelic (odds ratio (OR) = 1.02; 95% confidence interval (CI): 0.91-1.14; P = 0.739) and dominant (OR = 0.97; 95% CI: 0.78-1.21; P = 0.803) models. Stratified analysis by ethnicity demonstrated a significant association in Asians. We conclude that the XRCC3 gene rs861539 polymorphism was associated with the risk for gastric cancer in Asian populations.

  1. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and susceptibility to depression in Asian population: a systematic meta-analysis.

    PubMed

    Rai, V

    2014-01-01

    Genetic association studies on MTHFR C677 T polymorphism and depression have been repeatedly performed over the last two decades and results are generally inconsistent. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for depression in Asian population. The author performed a meta-analysis and pooled data from individual case-control studies that examined the association between C677T polymorphism and depression (meta-analysis: 13 studies, 1,120 cases and 1,688 controls).The pooled Odd Ratios (OR) were estimated by both fixed effects and random effects models. Overall, there was an association between MTHFR C677T polymorphism and increased risk of depression under five genetic models (OR T vs. C=1.44, 95% CI= 1.56-1.78, P=0.001; OR TT vs. CC= 1.78, 95% CI 1.17– 2.69, P=0.006; OR CT vs CC=1.102, 95% CI=0.91-1.32,P=0.31; OR TT vs. CT+CC=1.73, 95% CI= 0.87-3.41, P=0.11; OR TT+CT vs. CC=1.26, 95% CI=0.96-1.64, P=0.08). Sensitivity analysis suggested exclusion of any single study did not alter the overall pooled Ors. In conclusion results of present meta-analysis supports that there is a significant association between MTHFR C677T polymorphism and depression risk, and MTHFR 677T allele contributes to increased risk of depression in Asian individuals.

  2. Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men.

    PubMed

    Harris, T P; Gomas, K P; Weir, F; Holyoake, A J; McHugh, P; Wu, M; Sin, Y; Sin, I L; Sin, F Y T

    2006-06-01

    CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLgamma) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLgamma in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non-normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLgamma CAG repeat lengths, =10/ not equal 10 heterozygotes and not equal 10/ not equal 10 homozygotes, were significantly different between normozoospermic and non-normozoospermic men (p < 0.05), with non-normozoospermic men having a slightly higher frequency of the =10/=10 genotypes. The allelic frequency for =10 is 0.79 and not equal10 is 0.21 for normozoospermic men and 0.85 and 0.15, respectively, for non-normozoospermic men (p < 0.025). There was no mutation detected in the exonuclease motifs in all the samples tested. Eighty normozoospermic and 124 non-normozoospermic semen samples were analysed for nucleotide substitutions in mitochondrial genes by PCR and sequencing. Heteroplasmic mutations were found in one azoospermic man, four asthenozoospermic men and two normozoospermic men. Only one asthenozoospermic man was heterozygous for the POLgamma genotype. Of the 17 men with non-synonymous nucleotide substitutions, 14 were homozygous for the POLgamma genotype. Non-normozoospermic men had twice as many nucleotide substitutions than normozoospermic men. However, there were no significant differences in the frequencies of nucleotide substitution and POLgamma genotypes in the two groups of men.

  3. Analysis of Gln223Agr Polymorphism of Leptin Receptor Gene in Type II Diabetic Mellitus Subjects among Malaysians

    PubMed Central

    Etemad, Ali; Ramachandran, Vasudevan; Pishva, Seyyed Reza; Heidari, Farzad; Aziz, Ahmad Fazli Abdul; Yusof, Ahmad Khairuddin Mohamed; Pei, Chong Pei; Ismail, Patimah

    2013-01-01

    Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05). PMID:24051404

  4. Meta-Analysis of Risk Association Between Interleukin-17A and F Gene Polymorphisms and Inflammatory Diseases.

    PubMed

    Eskandari-Nasab, Ebrahim; Moghadampour, Mehdi; Tahmasebi, Arezoo

    2017-04-01

    This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease. PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct were searched, and odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the strength of the association. A total of 25 studies comprising 7,474 cases and 10,628 controls were included. Significant associations were found between inflammatory diseases and IL-17A rs2275913 A versus G allele (OR = 1.197, P = 0.033) and the GA versus GG genotype in the codominant model (OR = 1.406, P = 0.036). Our findings suggested that individuals who carry the rs2275913 A allele or GA genotype have a 20% or 41%-increased risk of inflammatory diseases compared with subjects with the G allele or GG genotype, respectively. With respect to IL-17F rs763780, the C versus T allele (OR = 1.94; P = 0.040), the TC versus TT (OR = 1.39; P = 0.041), the CC versus TT (OR = 2.71; P = 0.003), as well as the TC + CC versus TT genotype (OR = 1.83; P = 0.032) were risk factors for RA. In summary, our pooled analysis indicated that the IL-17A (rs2275913) and IL17F (rs763780 T/C) increased the RA risk.

  5. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

    PubMed

    Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

    2016-01-01

    Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

  6. Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region.

    PubMed

    Shink, Eric; Harvey, Mario; Tremblay, Monique; Gagné, Bernard; Belleau, Pascal; Raymond, Catherine; Labbé, Michel; Dubé, Marie-Pierre; Lafrenière, Ronald G; Barden, Nicholas

    2005-05-05

    Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers D12S86 and D12S378 on chromosome 12 was the most probable genomic region to contain a susceptibility gene for affective disorders. Here we present a more detailed genetic analysis of a 7.7 Mb genomic region located on 12q24.31. This region was saturated with 20 microsatellite markers to refine the candidate region and linkage analysis performed in 41 families from the Saguenay-Lac-St-Jean (SLSJ) region of Quebec. The results of two point parametric analysis using MFLINK supported the presence of a susceptibility locus on chromosome 12q24.31. Association studies with microsatellite markers using a case/control sample from the same population (n = 401) and analyzed with CLUMP revealed significant allelic associations between the bipolar phenotype and markers NBG6 (P = 0.008) and NBG12 (P < 10(-3)). According to these results, we investigated candidate genes in the NBG12 area. We analyzed 32 genes for the presence of polymorphisms in coding sequences and intron/exon junctions and genotyped 22 non-synonymous SNPs in the SLSJ case/control sample. Two uncommon polymorphisms (minor allele frequency < or = 0.03) found in KIAA1595 and FLJ22471 genes, gave P-values below 0.05 with the T1 statistic. Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene. These results do not give strong support for a role in the susceptibility to bipolar disorder of any of these genes analyzed. However, the significance of rare polymorphisms should be explored by further analyses. Copyright 2005 Wiley-Liss, Inc.

  7. Polymorphisms of the insertion / deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data.

    PubMed

    Mondry, Adrian; Loh, Marie; Liu, Pengbo; Zhu, Ai-Ling; Nagel, Mato

    2005-01-11

    Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies. The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used. No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P = .08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype. The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with

  8. An Updated Meta-Analysis of the Effects of the Endothelial Nitric Oxide synthase Gene G894T Polymorphism and Erectile Dysfunction Risk.

    PubMed

    Dai, Feng; Zhu, Lijie; Mi, Yuanyuan; Feng, Ninghan

    2015-07-01

    Erectile dysfunction (ED) is a common disorder leading to a serious and negative impact on the patient's quality of life. The gene encoding endothelial nitric oxide synthase (eNOS) is an interesting candidate gene for understanding the physiopathology of ED. However, an association between eNOS G894T polymorphism and ED risk is uncertain and should be updated. Therefore, a meta-analysis of the current literature was necessary to clarify this relationship. We searched Pubmed and China National Knowledge Infrastructure (CNKI) (last search updated on Dec 12, 2013) using 'nitric oxide synthase,' 'polymorphism or variant,' 'genotype,' and 'ED' as keywords. We also searched reference lists of studies corresponding to the inclusion criteria for the meta-analysis. These studies involved the total number of 1,445 ED men and 1,459 healthy control men subjects. Odds ratio (OR) and 95 % confidence intervals (CIs) were used to evaluate this relationship. Statistical analysis was performed with STATA10.0. In the overall analysis, significantly decreased associations between ED risk and eNOS G894T polymorphism were found. Moreover, in the subgroup analysis based on ethnicity, similar significant associations were detected in both Caucasians (such as GG+GT vs. TT: OR 0.92, 95 %CI 0.86-0.97) and Asians (such as GG+GT vs. TT: OR 0.24, 95 % CI 0.07-0.85). The Egger's test did not reveal the presence of a publication bias. Our investigations demonstrate that eNOS G894T polymorphism might protect men against ED risk. Further studies based on larger sample size and gene-environment interactions should be conducted.

  9. Folate and Breast Cancer: Role of Intake, Blood Levels and Metabolic Gene Polymorphisms

    DTIC Science & Technology

    2003-06-01

    those with MTHFR , MTR, and MTRR polymorphisms. The specific aims of this postdoctoral training proposal are 1) further methodological training in the...analysis of gene-gene and gene-environment interactions by studying folate intake and folate metabolic gene polymorphisms ( MTHFR , MTR, MTRR) using data

  10. Lack of an association between Paraoxonase 1 gene polymorphisms (Q192R, L55M) and Alzheimer's disease: a meta-analysis.

    PubMed

    Pi, Yan; Zhang, Lili; Chang, Kai; Li, Binghu; Guo, Lu; Fang, Chuanqin; Gao, Changyue; Wang, Jingzhou; Xiang, Jing; Li, Jingcheng

    2012-08-15

    The association between Paraoxonase 1 (PON1) gene polymorphisms (Q192R, L55M) and Alzheimer's disease (AD) risk has been reported inconsistent results. To assess the association between PON1 polymorphisms and AD risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, a total of 10 studies including 3081 AD cases and 3054 controls were identified. The pooled odds ratio (OR) with 95% confidence interval (95% CI) were performed. There was no significant association between PON1 Q192R polymorphism and AD risk in all comparison models (R vs. Q, OR=0.89, 95% CI=0.82-0.96; RR vs. QQ, OR=0.83, 95% CI=0.68-1.01; RR+RQ vs. QQ, OR=0.86, 95% CI=0.75-0.97; and RR vs. QR+QQ, OR=0.94, 95% CI=0.81-1.11). For the PON1 L55M polymorphism, lack of an association was also found (L vs. M, OR=0.95, 95% CI=0.86-1.05; LL vs. MM, OR=0.67, 95% CI=0.51-0.88; LL vs. ML+MM, OR=0.82, 95% CI=0.69-0.98; and LL+ML vs. MM, OR=0.75, 95% CI=0.58-0.96). On subgroup analysis by ethnicity, similar results were found. Conclusively, the present meta-analysis revealed that PON1 gene polymorphisms (Q192R, L55M) were unlikely to contribute to AD susceptibility. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population.

    PubMed

    Muslumanoglu, Muhammed H; Tepeli, Emre; Demir, Selma; Uludag, Ahmet; Uzun, Derya; Atli, Engin; Canturk, Kemal M; Ozdemir, Muhsin; Turgut, Mehmet

    2009-10-01

    Prostate cancer is the most common cause of cancer deaths in men and is a major health problem worldwide. Methylene tetrahydrofolate reductase (MTHFR) plays an important role for folate metabolism and is also an important source for DNA methylation and DNA synthesis (nucleotide synthesis). The objective of this study was to investigate the relationship between the A1298C and C677T polymorphisms of the MTHFR gene and prostate cancer in the Turkish population. In our study, 93 prostate cancer patients between the ages of 50-89 and a control group of 166 benign prostate hyperplasia patients were evaluated. C677T and A1298C polymorphism ratios were compared among these two groups, and an analysis was made to see if there is a statistically meaningful difference. In this study, it has been observed that C677T polymorphism of the MTHFR gene produces no statistically significant difference for T allele frequency and the genotype frequency in prostate cancer patients and male controls with benign prostate hyperplasia not having prostate cancer, whereas it has been observed that A1298C polymorphism produces a statistically significant difference for C allele frequency in prostate cancer patients and controls and that it also produces a statistically marginal significance for genotype frequencies.

  12. Lack of any association between insertion/deletion (I/D) polymorphisms in the angiotensin-converting enzyme gene and digestive system cancer risk: a meta-analysis.

    PubMed

    Liu, Jin-Fei; Xie, Hao-Jun; Cheng, Tian-Ming

    2013-01-01

    To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.

  13. SOD2 gene Val16Ala polymorphism is associated with macroalbuminuria in Mexican Type 2 Diabetes patients: a comparative study and meta-analysis

    PubMed Central

    2013-01-01

    Background Several studies in type 2 diabetes patients have shown significant associations between the SOD2 gene Val16Ala polymorphism and albuminuria, but this association has not been explored in the Mexican population. Methods We evaluated the association between the SOD2 gene Val16Ala polymorphism (rs4880) and macroalbuminuria in a sample of 994 unrelated Mexican type 2 diabetes patients. The study included 119 subjects with urinary albumin >300 mg/dL and 875 subjects with urinary albumin ≤ 30 mg/dL. Genotyping of the SOD2 gene Val16Ala SNP was carried out with Real-Time Polymerase Chain Reaction (RT-PCR). Results The frequency of the TT genotype was 6.7% higher in participants with macroalbuminuria than in the normoalbuminuria group (16.8% vs. 10.1%). Using a logistic regression analysis, we observed that individuals with the CC genotype had significantly lower risks of macroalbuminuria than those with the TT genotype (OR=0.42, p=0.034). We carried out a meta-analysis combining our data with data from four previous studies and estimated an odds ratio (95% CI) for the C allele (with respect to the reference T allele) of 0.65 (0.52-0.80, p<0.001). Conclusions A significant association was found between the SOD2 Val16Ala polymorphism and macroalbuminuria in a sample of Mexican type 2 diabetes patients. PMID:24119114

  14. Roles of osteopontin gene polymorphism (rs1126616), osteopontin levels in urine and serum, and the risk of urolithiasis: a meta-analysis.

    PubMed

    Li, Xiao; Liu, Kang; Pan, Yongsheng; Zhang, Jing; Lv, Qiang; Hua, Lixin; Wang, Zengjun; Li, Jie; Yin, Changjun

    2015-01-01

    Objective. Previous studies have investigated the relationships between osteopontin gene polymorphism rs1126616 and OPN levels and urolithiasis, but the results were controversial. Our study aimed to clarify such relationships. Methods. A meta-analysis was performed by searching the databases Pubmed, Embase, and Web of Science for relevant studies. Crude odds ratios (ORs) or standardised mean differences with 95% confidence intervals (CIs) were calculated to evaluate the strength of association. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results. Overall, a significantly increased risk of urolithiasis was associated with OPN gene polymorphism rs1126616 for all the genetic models except recessive model. When stratified by ethnicity, the results were significant only in Turkish populations. For OPN level association, a low OPN level was detected in the urine of urolithiasis patients in large sample size subgroup. Results also indicated that urolithiasis patients have lower OPN level in serum than normal controls. Conclusion. This meta-analysis revealed that the T allele of OPN gene polymorphism increased susceptibility to urolithiasis. Moreover, significantly lower OPN levels were detected in urine and serum of urolithiasis patients than normal controls, thereby indicating that OPN has important functions in the progression of urolithiasis.

  15. Genetic susceptibility to renal scar formation after urinary tract infection: a systematic review and meta-analysis of candidate gene polymorphisms.

    PubMed

    Zaffanello, Marco; Tardivo, Stefano; Cataldi, Luigi; Fanos, Vassilios; Biban, Paolo; Malerba, Giovanni

    2011-07-01

    Identifying patients who may develop renal scarring after urinary tract infections (UTI) remains challenging, as clinical determinants explain only a portion of individual risk. An additional factor that likely affects risk is individual genetic variability. We searched for peer-reviewed articles from 1980 to December 2009 in electronic databases that reported results showing an association between gene polymorphims and renal scaring after UTI. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality using an aggregate scoring system. The 18 studies ultimately included in the review had investigated 16 polymorphisms in nine genes in association with renal scarring formation after UTI. Based on the predetermined criteria for assessing the quality of the studies, 12 studies (67%) were identified as being of poor quality design. A meta-analysis of cumulative studies showed on association between renal scarring formation after UTI and the angiotensin converting enzyme insertion/deletion polymorphism [ACE I/D; recessive model for D allele; odds ratio (OR) 1.73, 95% confidence interval (CI) 1.09-2.74, P = 0.02] or transforming growth factor (TGF)-β1 c.-509 T > C polymorphism (dominant model for T allele; OR 2.24, 95% CI 1.34-3.76, P = 0.002). However, heterogeneity among studies was large, indicating a strong difference that cannot only be explained by differences in study design. The studies reviewed in this article support a modest involvement of the vasomotor and inflammatory genes in the development of renal scarring after UTIs. This review also shows that only few possible candidate genes have been investigated for an association with renal scarring, raising the hypothesis that some gene polymorphisms may exert their effects through an interaction with as yet uninvestigated factors that may be related to geographic and/or socio-economic differences.

  16. Increased risks between Interleukin-10 gene polymorphisms and haplotype and head and neck cancer: a meta-analysis.

    PubMed

    Niu, Yu-Ming; Du, Xin-Ya; Cai, Heng-Xing; Zhang, Chao; Yuan, Rui-Xia; Zeng, Xian-Tao; Luo, Jie

    2015-11-27

    Molecular epidemiological research suggests that interleukin-10 (IL-10) polymorphisms may be associated with an increased risk of head and neck cancer (HNC), but results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on genetic polymorphisms of IL-10. PubMed, Embase, CNKI and Wanfang databases were searched for studies that examined the relationship between IL-10 polymorphisms or haplotypes and HNC risk. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the relationship strength. Publication bias, sensitivity and cumulative analyses were conducted to measure the robustness of our findings. Overall, nine related studies involving 2,258 patients and 2,887 control samples were analyzed. Significant associations between the IL-10-1082A > G polymorphism and HNC risk were observed (G vs. A: OR = 1.56, 95% CI = 1.27-1.92, P < 0.01, I(2) = 69.4%; AG vs. AA: OR = 1.64, 95% CI = 1.32-2.05, P < 0.01, I(2) = 55.6%; GG vs. AA: OR = 2.24, 95% CI = 1.69-2.97, P < 0.01, I(2) = 38.5%; AG + GG vs. AA: OR = 1.70, 95% CI = 1.36-2.14, P = 0.02, I(2) = 61.8%; GG vs. AA + AG: OR = 1.89, 95% CI = 1.23-2.90, P = 0.01, I(2) = 46.3%) in the total population, as well as in subgroup analysis. Moreover, increased HNC risks were also associated with the IL-10 -819T > C polymorphism and the GCC haplotype. In conclusion, our meta-analyses suggest that IL-10 polymorphisms, specifically the -1082A > G polymorphism, may be associated with increased risk of HNC development.

  17. Lack of association between the 389C>T polymorphism (rs769217) in the catalase (CAT) gene and the risk of vitiligo: an update by meta-analysis.

    PubMed

    He, Jie; Li, Xiaoyan; Li, Yunhui; Ren, Bocheng; Sun, Jian; Zhang, Wei; Li, Wancheng

    2015-08-01

    The catalase (CAT) T/C at codon 389 in the exon 9 polymorphism has been implicated in susceptibility to vitiligo but a large number of studies have reported inconclusive results. The purpose of this study is to evaluate the association between the catalase gene polymorphism (389C>T) and the risk of vitiligo. A meta-analysis was carried out to analyse the association between 389C>T and vitiligo risk. Eight case-control studies with 2923 cases and 4237 controls were included in the meta-analysis. The results indicated that there was no association between this polymorphism and vitiligo (TT + CT versus CC: OR = 1.08, 95% CI = 0.98-1.20, P = 0.11, T versus C: OR = 1.07, 95% CI = 0.99-1.16, P = 0.092). In a subgroup analysis by ethnicity, no significant association between the CAT gene 389C>T polymorphism and vitiligo susceptibility was found in Caucasians (TT + CT versus CC: OR = 1.15, 95% CI = 0.98-1.35, P = 0.08; T versus C: OR = 1.07, 95% CI = 0.97-1.19, P = 0.173) and Asians (TT + CT versus CC: OR = 1.12, 95% CI =0.93-1.34, P = 0.23; T versus C: OR = 1.07, 95% CI = 0.94-1.21, P = 0.321). Our results suggest that 389C>T may not contribute to vitiligo susceptibility. However, larger primary studies with the consideration of gene-environment and gene-gene interactions are still required to further evaluate the interaction of CAT gene polymorphism with vitiligo susceptibility. © 2014 The Australasian College of Dermatologists.

  18. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val and susceptibility to ovary cancer: a systematic review and meta-analysis.

    PubMed

    Pan, Xinwei; Lu, Yan; Long, Ying; Yao, Desheng

    2014-03-01

    Many studies have reported the role of methylenetetrahydrofolate reductase (MTHFR) gene Ala222Val polymorphism with ovary cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR Ala222Val polymorphism and ovary cancer risk. A total of 8 studies including 3,723 cases and 4,001 controls were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, no significant association between ovary cancer risk and MTHFR Ala222Val polymorphism was found in all genetic models [codominant model: OR = 0.980, 95% CI = 0.756-1.270, P h = 0.088, P = 0.877; dominant model: OR = 1.022, 95% CI = 0.864-1.208, P h = 0.033, P = 0.803; recessive model: OR = 1.050, 95% CI = 0.803-1.373, P h = 0.032, P = 0.723; allele comparison model: OR = 1.028, 95% CI = 0.898-1.178, P h = 0.012, P = 0.685]. In the stratified analysis by ethnicity, no evidence of any associations of this polymorphism with ovary cancer was found in the Caucasian populations. Our meta-analysis supports that the MTHFR Ala222Val polymorphism is not contributed to the risk of ovary cancer from currently available evidence.

  19. The association of three promoter polymorphisms in interleukin-10 gene with the risk for colorectal cancer and hepatocellular carcinoma: A meta-analysis

    PubMed Central

    Shi, Yan-Hui; Zhao, Dong-Mei; Wang, Yue-Fei; Li, Xue; Ji, Man-Ru; Jiang, Dan-Na; Xu, Bai-Ping; Zhou, Li; Lu, Chang-Zhu; Wang, Bin

    2016-01-01

    Mounting evidence supports a potent inhibitory role of interleukin-10 (IL-10) in tumor carcinogenesis, angiogenesis and metastasis. This meta-analysis was designed to examine the association of three promoter polymorphisms (−592C > A, −819C > T and −1082G > A) in IL-10 gene with the risk for colorectal cancer and hepatocellular carcinoma. Qualification assessment and data collection were completed by two authors independently. The random-effects model using the DerSimonian and Laird method was fitted by the STATA software. Twenty-five articles involving 5933 cases and 9724 controls were meta-analyzed. Overall comparisons of the mutant alleles (−592A, −819T and −1082A) of three promoter polymorphisms with alternative wild alleles failed to reveal any statistical significance for both colorectal cancer and hepatocellular carcinoma (P > 0.05), and the likelihood of heterogeneity was low (I2 < 50%). For −592C > A polymorphism, a significant risk for colorectal cancer was identified when analysis was restricted to East Asians (odds ratio or OR = 1.41, 95% confidence interval or CI: 1.18–1.68, P < 0.001) and retrospective studies (OR = 1.23, 95% CI: 1.09–1.39, P = 0.001). As weighed by the Egger’s test and the fill-and-trim method, there was a low probability of publication bias for all studied polymorphisms. Our findings collectively suggest that the −592C > A polymorphism in IL-10 gene might be a susceptibility locus for colorectal cancer in East Asians. PMID:27489033

  20. Polymorphism analysis of COL4A3 and COL4A4 genes in Greek patients with keratoconus.

    PubMed

    Kokolakis, Nikolaos S; Gazouli, Maria; Chatziralli, Irini P; Koutsandrea, Chryssanthi; Gatzioufas, Zisis; Peponis, Vasileios G; Droutsas, Konstantinos D; Kalogeropoulos, Christos; Anagnou, Nicholas; Miltsakakis, Dimitrios; Moschos, Marilita M

    2014-12-01

    In this study, we conducted the genotyping of D326Y in COL4A3 and M1327V, as well as F1644F in COL4A4 polymorphisms, in a case-control sample panel of Greek origin population. A case-control panel, with 45 keratoconus (KC) patients and 78 healthy controls, were surveyed. DNA from each individual was tested for the D326Y in COL4A3 and M1327V, as well as F1644F in COL4A4 polymorphisms by direct sequencing. When analyzing the Hardy-Weinberg equilibrium, we observed no significant deviation from expected numbers in both KC patients and controls. The genotype frequencies in the polymorphisms tested were not found to be significantly associated with KC development risk. The M1327V AA and F1644F TT genotypes were significantly over-represented in healthy individuals. We could hypothesize that mutations in COL4A3 and COL4A4 genes are not involved in KC risk in Greek population. Nevertheless, the M1327V AA and F1644F TT genotypes were significantly over-represented in healthy individuals, suggesting a protective role of these genotypes in KC development risk in our population.

  1. Geographical and Ethnic Distributions of the MTHFR C677T, A1298C and MTRR A66G Gene Polymorphisms in Chinese Populations: A Meta-Analysis

    PubMed Central

    Zeng, Dingyuan

    2016-01-01

    Background The geographical and ethnic distributions of the polymorphic methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) and methionine synthase reductase (MTRR) mutation (A66G) remain heterogeneous in China. The goal of this study was to estimate the pooled frequencies of the alleles and associated genotypes of these gene polymorphisms among healthy populations in Mainland China. Objective and Methods We systematically reviewed published epidemiological studies on the distributions of 3 genetic variants in Chinese healthy populations living in Mainland China through a meta-analysis. The relevant electronic databases were searched. All of the raw data of the eligible citations were extracted. The frequency estimates were stratified by geography, ethnicity and sex. Results Sixty-six studies were identified with a total of 92277 study participants. The meta-analysis revealed that the frequencies of the MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms varied significantly between different ethnic groups and along geographical gradients. The frequencies of the 677T allele and 677TT genotype increased along the southern-central-northern direction across Mainland China (all Pvalues≤0.001). The frequencies of the 1298C, 1298CC, 66G and 66GG genotypes decreased along the south-central-north direction across the country (all Pvalues≤0.001). Conclusions Our meta-analysis strongly indicates significant geographical and ethnic variations in the frequencies of the C677T, A1298C, and A66G gene polymorphisms in the folate metabolism pathway among Chinese populations. PMID:27089387

  2. MTHFR C677T, A1298C and MS A2756G Gene Polymorphisms and Male Infertility Risk in a Chinese Population: A Meta-Analysis

    PubMed Central

    Yang, Bo; Fang, Kun; Ren, Shangqing; Liao, Jian; Liu, Shengzhuo; Liu, Liangren; Peng, Zhufeng; Dong, Qiang

    2017-01-01

    Background Methylenetetrahydrofolate reductase gene (MTHFR C677T and A1298C) and methionine synthase gene (MS A2756G) polymorphisms have shown an association with male infertility risk in several ethnic populations. Although several studies have evaluated these associations in Chinese populations, their small sample sizes and inconsistent outcomes have prevented strong conclusions. Therefore, the present meta-analysis was performed with published studies to evaluate the associations of the three single nucleotide polymorphisms (SNPs) and male infertility in a Chinese population. Methods We conducted a search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature (CBM), VIP, and Chinese literature (Wan Fang) databases up to May 31, 2016. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to assess the strength of associations with a random-effect model or a fixed-effect model based on the heterogeneity analysis results. Sensitivity analysis was used to confirm the reliability and stability of the meta-analysis. Results A total of nine studies, including 1,713 cases and 1,104 controls, were included in the meta-analysis. The pooled results indicated that the MTHFR C667T polymorphism was significantly associated with increased risk of male infertility in the Chinese population in the allele model (T vs. C: OR = 1.47, 95%CI = 1.32–1.63), the dominant model (TT + CT vs. CC: OR = 1.51, 95%CI = 1.30–1.77), the additive model (TT vs. CC: OR = 2.08, 95%CI = 1.68–2.58) and the recessive model (TT vs. CT+CC: OR = 1.58, 95%CI = 1.31–1.90), whereas the MTHFR A1298C and MS A2756G polymorphisms were not risk factors. There was no significant heterogeneity in any genotype contrasts among the studies. The sensitivity analysis indicated that the results of this meta-analysis were relatively stable. Conclusion This study suggests that the MTHFR C667T polymorphism may contribute to the genetic

  3. [Meta-analysis on relationship between single nucleotide polymorphism of rs2231142 in ABCG2 gene and gout in East Asian population].

    PubMed

    Wu, Lei; He, Yao; Zhang, Di

    2015-11-01

    To systematically evaluate the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout in East Asian population. The literature retrieval was conducted by using English databases (Medline, EMbase), Chinese databases (CNKI, Vip, Wanfang, SinaMed) and others to collect the published papers on the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout by the end of December 2014. Meta-analysis was performed with software Stata 12.0. Nine studies were included. There were significant associations between increased risk of gout and single nucleotide polymorphism of rs2231142, the combined OR was 2.04 (95%CI: 1.82-2.28) for A allele and C allele, 1.97 (95%CI: 1.57-2.48) for CA and CC, 3.71 (95%CI: 3.07-4.47) for AA and CC. Sex and region specific subgroup analysis showed less heterogeneity. There is significant association between gout and single nucleotide polymorphism of rs2231142 in East Asian population, and A allele is a high risk gene for gout.

  4. Analysis of Clostridium botulinum Serotype E Strains by Using Multilocus Sequence Typing, Amplified Fragment Length Polymorphism, Variable-Number Tandem-Repeat Analysis, and Botulinum Neurotoxin Gene Sequencing▿

    PubMed Central

    Macdonald, Thomas E.; Helma, Charles H.; Shou, Yulin; Valdez, Yolanda E.; Ticknor, Lawrence O.; Foley, Brian T.; Davis, Stephen W.; Hannett, George E.; Kelly-Cirino, Cassandra D.; Barash, Jason R.; Arnon, Stephen S.; Lindström, Miia; Korkeala, Hannu; Smith, Leonard A.; Smith, Theresa J.; Hill, Karen K.

    2011-01-01

    A total of 41 Clostridium botulinum serotype E strains from different geographic regions, including Canada, Denmark, Finland, France, Greenland, Japan, and the United States, were compared by multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) analysis, variable-number tandem-repeat (VNTR) analysis, and botulinum neurotoxin (bont) E gene sequencing. The strains, representing environmental, food-borne, and infant botulism samples collected from 1932 to 2007, were analyzed to compare serotype E strains from different geographic regions and types of botulism and to determine whether each of the strains contained the transposon-associated recombinase rarA, involved with bont/E insertion. MLST examination using 15 genes clustered the strains into several clades, with most members within a cluster sharing the same BoNT/E subtype (BoNT/E1, E2, E3, or E6). Sequencing of the bont/E gene identified two new variants (E7, E8) that showed regions of recombination with other E subtypes. The AFLP dendrogram clustered the 41 strains similarly to the MLST dendrogram. Strains that could not be differentiated by AFLP, MLST, or bont gene sequencing were further examined using three VNTR regions. Both intact and split rarA genes were amplified by PCR in each of the strains, and their identities were confirmed in 11 strains by amplicon sequencing. The findings suggest that (i) the C. botulinum serotype E strains result from the targeted insertion of the bont/E gene into genetically conserved bacteria and (ii) recombination events (not random mutations) within bont/E result in toxin variants or subtypes within strains. PMID:22003031

  5. Analysis of RANKL gene polymorphism (rs9533156 and rs2277438) in Iranian patients with chronic periodontitis and periimplantitis.

    PubMed

    Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Gholami, Gholam Ali; Khosravi, Alireza; Tabari, Zahra Alizadeh

    2013-05-01

    RANK/OPG/RANKL pathway plays a significant role in osteoclastogenesis, osteoclast activation, and regulation of bone resorption. The aim of this study was to investigate the association of RANKL gene polymorphisms (rs9533156 and rs2277438) with chronic periodontitis and peri-implantitis in an Iranian population. 77 patients with chronic periodontitis, 40 patients with peri-implantitis and 89 periodontally healthy patients were enrolled in this study. 5cc of blood was obtained from the cephalic vein of subjects arms and transferred into tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Differences in the frequencies of genotypes and alleles in the disease and control groups were analyzed using Chi-square and Fisher's exact statistical tests. Comparison of frequency of alleles in SNP rs9533156 of RANKL gene between the chronic periodontitis group with the control and peri-implantitis groups revealed statistically significant differences (P=0.024 and P=0.027, respectively). Comparison of genotype expression of SNP rs9533156 on RANKL gene between the peri-implantitis group with chronic periodontitis and control groups revealed statistically significant differences (P=0.001); the prevalence of CT genotype was significantly higher amongst the chronic periodontitis group. Regarding SNP rs2277438 of RANKL gene, comparison of prevalence of genotypes and frequency of alleles did not reveal any significant differences (P=0.641/P=0.537, respectively). The results of this study indicate that CT genotype of rs9533156 RANKL gene polymorphism was significantly associated with peri-implantitis, and may be considered as a genetic determinant for peri-implantitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis.

    PubMed

    Liu, Ai Ling; Xie, Hui Jun; Xie, Hong Yan; Liu, Jun; Yin, Jie; Hu, Jin Song; Peng, Cui Ying

    2017-08-21

    Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results. Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2. A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28-1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25-1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38-2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25-1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29-1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08-1.64, P = 0.008) CONCLUSION: This meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.

  7. The estrogen receptor α gene (XbaI, PvuII) polymorphisms and susceptibility to idiopathic scoliosis: a meta-analysis.

    PubMed

    Yang, Mingyuan; Li, Chao; Li, Ming

    2014-09-01

    A genetic association meta-analysis of estrogen receptor α gene (ERα) polymorphisms with idiopathic scoliosis. To determine whether the ERα gene polymorphisms correlate with idiopathic scoliosis. Idiopathic scoliosis represents a complex genetic trait under the influence of multiple predisposition genes. Several studies showed that single nucleotide polymorphism (SNP) in ERα was associated with idiopathic scoliosis, but the results from some studies were conflicting. We searched PubMed, EMBASE, and Cochrane CENTRAL databases from January 1994 to January 2014. All the case-control studies included should mainly study the relationship between XbaI A/G, PvuII T/C polymorphisms and the susceptibility of idiopathic scoliosis. A total of 299 articles were found, six of which fulfilled the inclusion criteria after being assessed by two reviewers. A pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations. Subgroup meta-analyses were performed according to ethnicity. Overall, ERα Xbal A/G polymorphism was not associated with risk of idiopathic scoliosis (G versus A, OR 1.07, 95% CI 0.88-1.30, P = 0.51; AG versus AA, OR 1.03, 95% CI 0.89-1.21, P = 0.67; GG versus AA, OR 1.12, 95% CI 0.72-1.73, P = 0.61; AG/GG versus AA, OR 1.05, 95% CI 0.91-1.22, P = 0.49; GG versus AG/AA, OR 1.10, 95% CI 0.75-1.63, P = 0.62). ERα PvuII T/C polymorphism was also not associated with risk of idiopathic scoliosis under five models (C versus T, OR 0.93, 95% CI 0.75-1.14, P = 0.48; TC versus TT, OR 0.99, 95% CI 0.80-1.23, P = 0.93; CC versus TT, OR 1.05, 95% CI 0.80-1.39, P = 0.72; TC/CC versus TT, OR 1.01, 95% CI 0.83-1.23, P = 0.93; CC versus TC/TT, OR 1.05, 95% CI 0.82-1.33, P = 0.72). ERα Xbal and ERα PvuII polymorphisms are not obviously associated with risk of idiopathic scoliosis.

  8. The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

    PubMed Central

    Xiu, Qing-yu

    2012-01-01

    Background A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Methods Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Results Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008). Conclusions This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma. PMID:22479620

  9. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    PubMed

    Nie, Wei; Li, Bing; Xiu, Qing-Yu

    2012-01-01

    A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008). This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  10. Association between C677T and A1298C polymorphisms of the MTHFR gene and risk of male infertility: a meta-analysis.

    PubMed

    Yang, Y; Luo, Y Y; Wu, S; Tang, Y D; Rao, X D; Xiong, L; Tan, M; Deng, M Z; Liu, H

    2016-04-26

    Published studies on the association between the C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene and male infertility risk are controversial. To obtain a more precise evaluation, we performed a meta-analysis based on published case-control studies. We conducted an electronic search of PubMed, EMBASE, the Cochrane Library, the Web of Science, and the China Knowledge Resource Integrated Database for papers on MTHFR gene C677T and A1298C polymorphisms and male infertility risk. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were used to assess the strength of association in homozygote, heterozygote, dominant, recessive, and additive models. Statistical heterogeneity, test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 13.0). Overall, 21 studies of C677T (4505 cases and 4024 controls) and 13 studies of A1298C (2785 cases and 3094 controls) were included in this meta-analysis. For C677T, the homozygote comparison results were OR = 1.629, 95%CI (1.215- 2.184), and the recessive model results were OR = 1.462 (1.155- 1.850). For A1298C, the homozygote comparison results were OR = 1.289 (1.029-1.616), and the recessive model results were OR = 1.288 (1.034-1.604). In conclusion, the current meta-analysis showed that the MTHFR C677T polymorphism was associated with a significantly increased male infertility risk in the Asian and overall populations, but not in the Caucasian population, and there was a significant association between the A1298C polymorphism and male infertility risk in the Asian, Caucasian, and overall groups.

  11. The associations between MDM4 gene polymorphisms and cancer risk

    PubMed Central

    Xu, Xiao-Liang; Yao, Guo-Liang; Liu, Rui-Ping; Zhao, Hui

    2016-01-01

    Considerable studies have investigated the associations between MDM4 gene polymorphisms and cancer risk recently, but with contradictory results. The aim of this meta-analysis was to evaluate the associations between MDM4 gene polymorphisms and cancer risk. Relevant studies were identified by a systematic search of PubMed, Embase, and CNKI databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the associations. Fifty-six studies published in 11 publications involving 18,910 cases and 51,609 controls were included in this meta-analysis. Five MDM4 gene polymorphisms were evaluated: rs4245739, rs1563828, rs11801299, rs10900598, and rs1380576. Our analyses suggested that the rs4245739 polymorphism was significantly associated with overall cancer risk. Furthermore, stratification analyses of ethnicity indicated that rs4245739 decreased the risk of cancer among the Asian population, and stratification analyses of smoking status indicated that rs4245739 decreased the risk of cancer among nonsmokers. However, stratification analyses of cancer type and sex suggested that rs4245739 was not related to cancer risk. There were no associations of rs1563828, rs11801299, rs10900598, or rs1380576 with overall cancer risk. In conclusion, our analyses indicated that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer. PMID:27742919

  12. Prion protein gene analysis in three kindreds with fatal familial insomnia (FFI): Codon 178 mutation and codon 129 polymorphism

    SciTech Connect

    Medori, R.; Tritschler, H.J. )

    1993-10-01

    Fatal familial insomnia (FFI) is a disease linked to a GAC(Asp) [yields] AAC(Asn) mutation in codon 178 of the prion protein (PrP) gene. FFI is characterized clinically by untreatable progressive insomnia, dysautonomia, and motor dysfunctions and is characterized pathologically by selective thalamic atrophy. The authors confirmed the 178[sup Asn] mutation in the PrP gene of a third FFI family of French ancestry. Three family members who are under 40 years of age and who inherited the mutation showed only reduced perfusion in the basal ganglia on single photon emission computerized tomography. Some FFI features differ from the clinical and neuropathologic findings associated with 178[sup Asn] reported elsewhere. However, additional intragenic mutations accounting for the phenotypic differences were not observed in two affected individuals. In other sporadic and familial forms of Creutzfeldt-Jakob disease and Gerstmann-Straeussler syndrome, Met or Val homozygosity at polymorphic codon 129 is associated with a more severe phenotype, younger age at onset, and faster progression. In FFI, young and old individuals at disease onset had 129[sup Met/Val]. Moreover, of five 178[sup Asn] individuals who are above age-at-onset range and who are well, two have 129[sup Met] and three have 129[sup Met/Val], suggesting that polymorphic site 129 does not modulate FFI phenotypic expression. Genetic heterogeneity and environment may play an important role in inter- and intrafamilial variability of the 178[sup Asn] mutation. 32 refs., 5 figs., 1 tab.

  13. [Polymorphisms of apoB gene 3' VNTR alleles and analysis of lipid level in Tibetan population].

    PubMed

    Chen, B; Zhao, Y; Cheng, Y

    1999-07-01

    To study the distribution and frequency of apoB gene 3' end alleles and try to find if there is any association with the level of plasma lipids. PCR and gradient polyacrylamide gel electrophoresis were used to analysize the chromsome DNA and PCR products. Totally 20 alleles were found in the Tibetan group and the distribution of alleles was bimode. The HVE32 and HVE34 were most common, and the frequencies of HVE32 and HVE34 were 0.27 and 0.21 respectively. Polymorphism apoB gene resides not only in the variable numbers of the repeat unit, but also in the variation in the oligonucleotide sequence within the repeat units as well as the variation in the arrangement of the repeat units.

  14. Molecular phylogenetic relationships of puffer fish inferred from partial sequences of cytochrome b gene and restriction fragment length polymorphism analysis.

    PubMed

    Hsieh, Yu-Wen; Hwang, Deng-Fwu

    2004-06-30

    Phylogenetic relationships among puffer fish were investigated by comparing cytochrome b gene sequences and restriction endonuclease assays of 16 species from Taiwan. DNA was prepared for sequencing by PCR. No variation in sequences was detected among individuals within each species. Direct estimates of mitochondrial cytochrome b gene sequence divergence among 16 puffer fish were from 3.41 to 31.78%. Different restriction patterns were found among 16 puffer fish with 10 restriction endonucleases, whereas no variation in patterns was detected among individuals within each species. The polymorphisms obtained by RFLP have provided a new set of genetic markers for the accurate identification of sibling puffer species. It is the first molecularly based study of puffer diversity and sheds light on the evolution and taxonomy of this major puffer fish family.

  15. Uridine diphosphate-glucuronosyltransferase 2B15 D85Y gene polymorphism is associated with lower prostate cancer risk: a systematic review and meta-analysis.

    PubMed

    Zhong, Xiao; Feng, Jiayu; Xiao, Ya; Wang, Pingxian; Fan, Qiming; Wu, Ronghua; Hu, Wengang; Huang, Chibing

    2017-08-08

    UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the UGT2B15 gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between UGT2B15 D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between UGT2B15 D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the UGT2B15 D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.

  16. Matrix metalloproteinase-2 -1306 C>T gene polymorphism is associated with reduced risk of cancer: a meta-analysis.

    PubMed

    Haque, Shafiul; Akhter, Naseem; Lohani, Mohtashim; Ali, Arif; Mandal, Raju K

    2015-01-01

    Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellular matrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP) at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association between MMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, a meta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306 C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2 -1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online web databases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancer cases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysis suggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637 to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) genetic models. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185, 95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179) models did not show any risk. No evidence of publication bias was detected during the analysis. The results of present meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reduced risk of cancer. However, further studies with consideration of different populations will be required to evaluate this relationship in more detail.

  17. Cytochrome P450 gene polymorphism and cancer.

    PubMed

    Agundez, Jose A G

    2004-06-01

    Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 gene polymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.

  18. Integrative analysis of single nucleotide polymorphisms and gene expression efficiently distinguishes samples from closely related ethnic populations

    PubMed Central

    2012-01-01

    Background Ancestry informative markers (AIMs) are a type of genetic marker that is informative for tracing the ancestral ethnicity of individuals. Application of AIMs has gained substantial attention in population genetics, forensic sciences, and medical genetics. Single nucleotide polymorphisms (SNPs), the materials of AIMs, are useful for classifying individuals from distinct continental origins but cannot discriminate individuals with subtle genetic differences from closely related ancestral lineages. Proof-of-principle studies have shown that gene expression (GE) also is a heritable human variation that exhibits differential intensity distributions among ethnic groups. GE supplies ethnic information supplemental to SNPs; this motivated us to integrate SNP and GE markers to construct AIM panels with a reduced number of required markers and provide high accuracy in ancestry inference. Few studies in the literature have considered GE in this aspect, and none have integrated SNP and GE markers to aid classification of samples from closely related ethnic populations. Results We integrated a forward variable selection procedure into flexible discriminant analysis to identify key SNP and/or GE markers with the highest cross-validation prediction accuracy. By analyzing genome-wide SNP and/or GE markers in 210 independent samples from four ethnic groups in the HapMap II Project, we found that average testing accuracies for a majority of classification analyses were quite high, except for SNP-only analyses that were performed to discern study samples containing individuals from two close Asian populations. The average testing accuracies ranged from 0.53 to 0.79 for SNP-only analyses and increased to around 0.90 when GE markers were integrated together with SNP markers for the classification of samples from closely related Asian populations. Compared to GE-only analyses, integrative analyses of SNP and GE markers showed comparable testing accuracies and a reduced number

  19. Identification of duck HSP70 gene, polymorphism analysis and tissue expression under control and heat stress conditions.

    PubMed

    Xia, M; Gan, J; Luo, Q; Zhang, X; Yang, G

    2013-01-01

    1. This study was designed to characterise the duck heat shock protein 70 gene (HSP70) and identify sequence variation. 2. Chicken HSP70 sequence (GenBank: AY143693) was used as a template to design a primer pair to amplify partial duck HSP70 gene. Primers were subsequently designed with the duck HSP70 gene as a template to amplify the complete duck HSP70 sequence. 3. Twelve commercial Sanshui White ducklings were subjected to a heat stress experiment. Tissue samples were collected for RNA extraction and real-time PCR to analyse the expression mechanism of duck HSP70. 4. A DNA pool was constructed from three different species for single nucleotide polymorphism (SNP) screening. The genotypes of the identified SNPs were detected in 145 Sanshui White ducklings. 5. Duck HSP70 gene was identified and characterised (GenBank: EU678246) and shown to contain no introns. Fifteen variations were identified within the open reading frame. Quantitative real-time PCR results showed that the expression of duck HSP70 gene was tissue specific and the highest expression level was seen in pectoral muscle.

  20. TGF-β1 Gene -509C/T Polymorphism and Coronary Artery Disease: An Updated Meta-Analysis Involving 11,701 Subjects

    PubMed Central

    Li, Yan-yan; Zhou, Yan-hong; Gong, Ge; Geng, Hong-yu; Yang, Xin-xing

    2017-01-01

    Background: The transforming growth factor-β1 (TGF-β1) gene -509C/T polymorphism has been suggested to be associated with increased coronary artery disease (CAD) risk. However, the individual studies results are still inconsistent. Objective and methods: To investigate the relationship between TGF-β1 gene -509C/T polymorphism and CAD, a meta-analysis involving 11,701 participants from 8 individual studies was conducted. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals were evaluated by using random or fixed effect models. Results: A significant association between TGF-β1 gene -509C/T polymorphism and CAD was detected in the total population under allelic (OR: 1.130, 95% CI: 1.060–1.200, P = 0.0001), recessive (OR: 1.390, 95% CI: 1.100–1.750, P = 0.006), dominant (OR: 0.857, 95% CI: 0.785–0.935, P = 2.507 × 10−4), homozygous (OR: 1.258, 95% CI: 1.098–1.442, P = 0.001), heterozygous (OR: 1.147, 95% CI: 1.046–1.257, P = 0.003), and additive genetic models (OR: 1.131, 95% CI: 1.063–1.204, P = 5.442 × 10−5). In the subgroup analysis, there was a significant association between them in Chinese population under all of the genetic models (P < 0.05), except under the heterozygous genetic model (P > 0.05). In the Caucasian subgroup, a significant association between them was also detected under all of the genetic models (P < 0.05), except under the recessive genetic model (P > 0.05). Conclusions: TGF-β1 gene -509C/T polymorphism was significantly associated with increased CAD risk. The people with T allele of TGF-β1 gene -509C/T polymorphism might be predisposed to CAD. PMID:28280469

  1. Polymorphism of the ovine calpastatin gene.

    PubMed

    Zhou, H; Hickford, J G H; Gong, H

    2007-06-01

    Calpastatin is a specific inhibitor of calpains and has been implicated in the regulation of beef tenderization. Variation in the ovine calpastatin gene (CAST) was investigated by amplification of a fragment containing the entire exon 6 using polymerase chain reaction (PCR), followed by single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. Five novel SSCP patterns, representing five different sequences, were identified. Either one or two different sequences were detected in individual sheep and all the sequences identified shared high homology to the published ovine and bovine CAST sequences, suggesting that these sequences represent allelic variants of the ovine CAST gene. Sequence analysis revealed a non-synonymous amino acid variation in exon 6, which would result in a Gln/Leu substitution in Domain L of the mature protein. Considerable variation was detected in an intron region close to the acceptor splice site, with both sequence variation and length variation being observed in this region. Variation detected here might have an impact on both the function and expression of ovine calpastatin.

  2. Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

    PubMed Central

    Hua, Rui-Xi; Zhu, Jinhong; Jiang, Dan-Hua; Zhang, Shao-Dan; Zhang, Jiang-Bo; Xue, Wen-Qiong; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Xeroderma pigmentosum group C (XPC) is a key component of the nucleotide excision repair (NER) pathway. Dysfunctional XPC protein may impair NER-mediated DNA repair capacity and further lead to genomic instability and carcinogenesis. Two common nonsynonymous polymorphisms in the XPC gene, Lys939Gln (rs2228001 A > C) and Ala499Val (rs2228000 C > T), have been investigated in various types of cancer. We genotyped these two polymorphisms in 1141 cases with histologically confirmed colorectal cancer (CRC) and 1173 healthy controls to explore their causative association with CRC susceptibility. Overall, no association was observed between these two variants and the risk of CRC. Our meta-analysis also confirmed a lack of overall association. Stratified analyses were performed by age, gender, smoking status, pack-year, drinking status, tumor sites, and Duke’s stages. We found that XPC Lys939Gln polymorphism was significantly associated with an increased CRC risk in subjects at 57 years of age or younger (adjusted odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.004–1.86, p = 0.047) and non-drinkers (adjusted OR = 1.53, 95% CI = 1.10–2.12, p = 0.011). Our results indicated that XPC Lys939Gln may be a low-penetrance CRC susceptibility polymorphism. Our findings warrant further validation. PMID:27669310

  3. Polymorphisms of candidate genes in Slovak autistic patients.

    PubMed

    Kelemenova, Silvia; Schmidtova, Eva; Ficek, Andrej; Celec, Peter; Kubranska, Aneta; Ostatnikova, Daniela

    2010-08-01

    Autism is one of the most genetically influenced neuropsychiatric disorders. However, its detailed genetic basis is far from being clear. Genome-wide association studies have revealed a number of candidate genes, mostly related to synaptogenesis and various neuroendocrine pathways. In our study we have focused on oxytocin (OT), oxytocin receptor (OXTR), GABA receptor gamma 3 (GABRG3), neuroligin (NLGN4X), and reelin (RELN). After signed consent, 90 autistic boys and 85 healthy controls were enrolled in the study. Polymorphisms of OT (rs2740204), OXTR (rs2228485), GABRG3 (rs28431127), and NLGN4X (rs5916338) were analyzed using restriction fragment length polymorphism. (GGC)n STR polymorphism in the 5' UTR of the RELN gene was genotyped using fragment analysis. The only significant association in autistic boys in Slovakia was found with higher number of GGC repeats in the RELN gene (P=0.001) potentially explaining lower RELN levels in blood and brain of autistic patients.

  4. Association between the DNA Repair Gene XRCC3 rs861539 Polymorphism and Risk of Osteosarcoma: a Systematic Review and Meta-Analysis

    PubMed

    Sobhan, Mohammad Reza; Forat Yazdi, Mohammad; Mazaheri, Mahta; Zare Shehneh, Masoud; Neamatzadeh, Hossein

    2017-02-01

    Objective: Although there are a few studies investigating the relation between X-Ray Repair Cross Complementing 3 (XRCC3) gene rs861539 polymorphism and osteosarcoma (OSA), the results are inconsistent. Therefore, we performed this systematic review and meta-analysis to clarify the associations between XRCC3 rs861539 polymorphism and OSA risk. Methods: We have retrieved published literature from PubMed, Google scholar, and ISI Web of Knowledge up to 25 January 2017. Odds ratios were pooled using either fixed-effects or random effects models. Overall and subgroup analyses were performed. Statistical analysis was performed running comprehensive meta-analysis (CMA) 2.0 software. Results: A total of four studies with 515 cases and 1,109 controls were identified in order to investigate the association between XRCC3 rs861539 polymorphism and OSA risk. The results showed that XRCC3 rs861539 polymorphism was associated with OSA in allelic (T vs. C: OR= 1.563, 95% CI: 1.244-1.963, p= <0.001), homozygote (TT vs. CC: OR= 2.574, 95% CI: 1.573-4.212, p= <0.001), dominant (TT+TC vs. CC: OR= 1.255, 95% CI: 1.011-1.558, p= 0.039), and recessive (TT vs. TC+CC: OR= 2.224, 95% CI: 1.393-3.552, p= 0.001), but not with heterozygote (TC vs. CC: OR= 1.361, 95% CI: 0.982-1.885, p= 0.064). The XRCC3 rs861539 polymorphism conferred susceptibility to OSA in Asians, but not in Caucasians. Additionally, we observed no evidence of publication bias. Conclusion: To the best of our knowledge, this is the first meta-analysis investigating the association between XRCC3 rs861539 polymorphism and OSA risk. Our results revealed a significant association between the XRCC3 rs861539 polymorphism and risk of OSA, especially in Asian populations. Future more comprehensive and well-designed case control studies with larger sample size are needed to warrant these findings.

  5. Association of CCND1 Gene c.870G>A Polymorphism with Breast Cancer Risk: A Case-ControlStudy and a Meta-Analysis.

    PubMed

    Soleimani, Zahra; Kheirkhah, Davood; Sharif, Mohammad Reza; Sharif, Alireza; Karimian, Mohammad; Aftabi, Younes

    2016-12-21

    Cyclin D1 (CCND1) plays an essential role in regulating the progress of the cell cycle from G1 to S phase. There is a common c.870G>A polymorphism in the CCND1 gene. The aim of this study was to investigate the association of CCND1 gene c.870G>A polymorphism with breast cancer risk in a case-control study, which followed by a meta-analysis and an in silico analysis. Three hundred and thirty-five subjects composed of 174 women with breast cancer and 161 healthy controls were included in the case-control study. CCND1 gene c.870G>A genotyping was performed by PCR-RFLP. Meta-analysis was done for 14 studies composed of 7281 cases and 6820 controls. Some bioinformatics tools were applied to investigate the effects of c.870G>A on the mRNA splicing and structure. Our data obtained from case-control study revealed that GA genotype (OR: 1.89, 95%CI: 1.12-3.17, p = 0.017), AA genotype (OR: 1.95, 95%CI: 1.08-3.53, p = 0.027), and A allele (OR: 1.44, 95%CI: 1.06-1.95, p = 0.019) were significantly associated with breast cancer risk. The results of meta-analysis showed a significant association between CCND1 c.870G>A polymorphism and breast cancer risk, especially in Caucasian population. In silico analysis revealed that c.870G>A transition affect CCND1 mRNA splicing and secondary structure.

  6. Association between Insulin-Like Growth Factor 1 Gene rs12423791 or rs6214 Polymorphisms and High Myopia: A Meta-Analysis

    PubMed Central

    Guo, Lan; Du, Xueying; Lu, Ciyong; Zhang, Wei-Hong

    2015-01-01

    Objective To evaluate the association of insulin-like growth factor 1 gene rs12423791 and rs6214 polymorphisms with high myopia. Methods An electronic search was conducted on PubMed, Embase, the Cochrane Library and the Chinese Biological Abstract Database for articles published prior to May 6, 2014. A meta-analysis was performed using Revman 5.1 and Stata 12.0, and the odds ratios with 95% confidence intervals were calculated in fixed or random effects models based on the results of the Q test. The subgroup analysis was conducted on the basis of the various regions, the sensitivity analysis was also performed to evaluate the stability of the results, and the publication bias was evaluated by a funnel plot and Egger’s linear regression analysis. Results This comprehensive meta-analysis included 2808 high myopia patients and 2778 controls from five unrelated studies. The results demonstrated that the significant association was not present in any genetic models between IGF-1 rs12423791 or rs6214 and high myopia. However, subgroup analysis indicated that rs12423791 polymorphism was associated with high myopia in the Chinese populations in the allelic contrast model (C vs. G: OR=1.24, 95% CI=1.04-1.48 in the fixed-effects model), the dominant model (CC+CG vs. GG: OR=1.40, 95% CI=1.16-1.69 in the fixed-effects model), and the codominant model (CG vs. GG: OR=1.37, 95% CI= 1.12-1.68 in the fixed-effects model). Additionally, none of the individual studies significantly affected the association between IGF-1 rs12423791 and high myopia, according to sensitivity analysis. Conclusion This meta-analysis shows that IGF-1 rs12423791 or rs6214 gene polymorphism is not associated with high myopia. PMID:26076017

  7. The Role of TP53 Gene Codon 72 Polymorphism in Leukemia: A PRISMA-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Ruan, Xiao-Lan; Li, Sheng; Meng, Xiang-Yu; Geng, Peiliang; Gao, Qing-Ping; Ao, Xu-Bin

    2015-09-01

    The purpose of this meta-analysis was aimed to evaluate the association of tumor protein p53 (TP53) gene codon 72 polymorphism with leukemia susceptibility. We searched PubMed to identify relevant studies, and 16 case-control studies from 14 published articles were identified as eligible studies, including 2062 leukemia patients and 5826 controls. After extracting data, odds ratio (OR) with the corresponding 95% confidence interval (95%CI) was applied to assess the association between TP53 codon 72 polymorphism and leukemia susceptibility. The meta-analysis was performed with the Comprehensive Meta-Analysis software, version 2.2. Overall, no significant association between TP53 codon 72 polymorphism and leukemia susceptibility was found in this meta-analysis (Pro vs Arg: OR = 1.05, 95%CI = 0.90-1.21; Pro/Pro vs Arg/Arg: OR = 1.13, 95%CI = 0.84-1.52; Arg/Pro vs Arg/Arg: OR = 0.94, 95%CI = 0.76-1.15; [Pro/Pro + Arg/Pro] vs Arg/Arg: OR = 0.99, 95%CI = 0.80-1.21; Pro/Pro vs [Arg/Arg + Arg/Pro]: OR = 1.19, 95%CI = 0.93-1.51). Similar results were also found in subgroup analysis by ethnicity, source of controls, and types of leukemia (either acute myeloid leukemia or acute lymphocytic leukemia). Our meta-analysis demonstrates that TP53 codon 72 polymorphism may not be a risk factor for acute leukemia; however, due to the limitations of this study, it should be verified in future studies.

  8. Sequence Variations in the Bovine Growth Hormone Gene Characterized by Single-Strand Conformation Polymorphism (Sscp) Analysis and Their Association with Milk Production Traits in Holsteins

    PubMed Central

    Yao, J.; Aggrey, S. E.; Zadworny, D.; Hayes, J. F.; Kuhnlein, U.

    1996-01-01

    Sequence variations in the bovine growth hormone (GH) gene were investigated by single strand conformation polymorphism (SSCP) analysis of seven amplified fragments covering almost the entire gene (2.7 kb). SSCPs were detected in four of these fragments and a total of six polymorphisms were found in a sample of 128 Holstein bulls. Two polymorphisms, a T->C transition in the third intron (designated GH4.1) and an A->C transversion in the fifth exon (designated GH6.2), were shown to be associated with milk production traits. GH4.1(c)/GH4.1(c) bulls had higher milk yield than GH4.1(c)/GH4.1(t) (P <= 0.005) and GH4.1(t)/GH4.1(t) (P <= 0.0022) bulls. GH4.1(c)/GH4.1(c) bulls had higher kg fat (P <= 0.0076) and protein (P <= 0.0018) than GH4.1(c)/GH4.1(t) bulls. Similar effects on milk production traits with the GH6.2 polymorphism were observed with the GH6.2(a) allele being the favorable allele. The average effects of the gene substitution for GH4.1 and GH6.2 are similar, with +/-300 kg for milk yield, +/-8 kg for fat content and +/-7 kg for protein content per lactation. The positive association of GH4.1(c) and GH6.2(a) with milk production traits may be useful for improving milk performance in dairy cattle. PMID:8978066

  9. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    PubMed

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  10. Songbird genomics: analysis of 45 kb upstream of a polymorphic Mhc class II gene in red-winged blackbirds (Agelaius phoeniceus).

    PubMed

    Gasper, J S; Shiina, T; Inoko, H; Edwards, S V

    2001-07-01

    Here we present the sequence of a 45 kb cosmid containing a previously characterized poly-morphic Mhc class II B gene (Agph-DAB1) from the red-winged blackbird (Agelaius phoeniceus). We compared it with a previously sequenced cosmid from this species, revealing two regions of 7.5 kb and 13.0 kb that averaged greater than 97% similarity to each another, indicating a very recent shared duplication. We found 12 retroelements, including two chicken repeat 1 (CR1) elements, constituting 6.4% of the sequence and indicating a lower frequency of retroelements than that found in mammalian genomic DNA. Agph-DAB3, a new class II B gene discovered in the cosmid, showed a low rate of polymorphism and may be functional. In addition, we found a Mhc class II B gene fragment and three genes likely to be functional (encoding activin receptor type II, a zinc finger, and a putative gamma-filamin). Phylogenetic analysis of exon 2 alleles of all three known blackbird Mhc genes indicated strong clustering of alleles by locus, implying that large amounts of interlocus gene conversion have not occurred since these genes have been diverging. Despite this, interspecific comparisons indicate that all three blackbird Mhc genes diverged from one another less than 35 million years ago and are subject to concerted evolution in the long term. Comparison of blackbird and chicken Mhc promoter regions revealed songbird promoter elements for the first time. The high gene density of this cosmid confirms similar findings for the chicken Mhc, but the segment duplications and diversity of retroelements resembles mammalian sequences.

  11. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies.

    PubMed

    Han, Liyuan; Zhang, Lina; Xing, Wenhua; Zhuo, Renjie; Lin, XiaLu; Hao, Yanhua; Wu, Qunhong; Zhao, Jinshun

    2014-01-01

    AIMS. Published data on the associations of VEGF polymorphisms with diabetic retinopathy (DR) susceptibility are inconclusive. A systematic meta-analysis was undertaken to clarify this topic. METHODS. Data were collected from the following electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science Direct, Excerpta Medica Database (EMBASE), and Cochrane Library with the last report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF-2578C/A (rs699947), -1154G/A (rs1570360), -460T/C (rs833061), -634G>C (rs2010963), and +936C/T (rs3025039) in at least two published studies. Meta-analysis was performed in a fixed/random effect model by using the software STATA 12.0. RESULTS. A total of 11 studies fulfilling the inclusion criteria were included in this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039) polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20-8.41, and P(z) = 0.01) in Asian and overall populations, while a significant association was also found between -460T/C (rs833061) polymorphism and DR risk under a recessive model (OR = 2.12, 95% CI = 1.12-4.01, and P(z) = 0.02). CONCLUSIONS. Our meta-analysis demonstrates that +936C/T (rs3025039) is likely to be associated with susceptibility to DR in Asian populations, and the recessive model of -460T/C (rs833061) is associated with elevated DR susceptibility.

  12. Antimicrobial susceptibility, virulence genes, and randomly amplified polymorphic DNA analysis of Staphylococcus aureus recovered from bovine mastitis in Ningxia, China.

    PubMed

    Wang, Dong; Zhang, Limei; Zhou, Xuezhang; He, Yulong; Yong, Changfu; Shen, Mingliang; Szenci, Otto; Han, Bo

    2016-12-01

    Staphylococcus aureusis the leading pathogen involved inbovine mastitis, but knowledgeabout antimicrobial resistance, virulence factors, and genotypes of Staphylococcus aureus resulting in bovine mastitis in Ningxia, China, is limited. Therefore, antimicrobial susceptibility, virulence gene, and randomly amplified polymorphic DNA (RAPD) analyses of Staph. aureus were carried out. A total of 327 milk samples from cows with clinical and subclinical mastitis in 4 regions of Ningxia were used for the isolation and identification of pathogens according to phenotypic and molecular characteristics. Antimicrobial susceptibility against 22 antimicrobial agents was determined by disk diffusion. The presence of 8 virulence genes in Staph. aureus isolates was tested by PCR. Genotypes of isolates were investigated based on RAPD. Results showed that 35 isolates obtained from mastitis milk samples were identified as Staph. aureus. The isolates were resistant to sulfamethoxazole (100%), penicillin G (94.3%), ampicillin (94.3%), erythromycin (68.6%), azithromycin (68.6%), clindamycin (25.7%), amoxicillin (11.4%), and tetracycline (5.7%). All of the isolates contained one or more virulence genes with average (standard deviation) of 6.6±1.6. The most prevalent virulence genes were hlb (97.1%), followed by fnbpA, hla, coa (94.3% each), nuc (85.7%), fnbpB (80%), clfA (77.1%), and tsst-1 (40%). Nine different gene patterns were found and 3 of them were the dominant gene combinations (77.1%). Staphylococcus aureus isolates (n=35) were divided into 6 genotypes by RAPD tying, the genotypes III and VI were the most prevalent genotypes. There was greatvariation in genotypes of Staph. aureus isolates, not only among different farms, but also within the same herd in Ningxia province. The study showed a high incidence of Staph. aureus with genomic variation of resistance genes, which is matter of great concern in public and animal health in Ningxia province of China.

  13. [Analysis on correlation between 3-hydroxy-3-methylglutary-coenzyme A reductase gene polymorphism of Glycyrrhiza uralensis and content of glycyrrhizic acid].

    PubMed

    Liu, Ying; Xu, Qiao-Xian; Wang, Xue-Yong; Liu, Chun-Sheng; Chen, Hong-Hao

    2012-12-01

    To reveal the 3-hydroxy-3-methylglutary-coenzyme A reductase (HMGR) gene polymorphism of Glycyrrhiza uralensis, and the correlation between HMGR gene polymorphism and the content of glycyrrhizic acid. Liquorice plants containing different content of glycyrrhizic acid were used as materials. RT-PCR was used to amplify their HMGR gene sequences, which were connected with vector pMD19-T for clone sequencing. Multiple alignments were performed to analyse HMGR gene polymorphism of G. uralensis. Then the correlation between HMGR gene polymorphism and the content of glycyrrhizic acid was revealed. HMGR gene sequences polymorphism included codon mutation, base substitution mutation, copy number polymorphism and allele heterozygosity. There were 4 types of mutations in HMGR gene coding amino acid sequences, namely -HSL, -HSV, GALLV, GALSV. Among them, -HSV type was common in liquorice plants, -HSL type only existed in liquorice plants with low content of glycyrrhizic acid, and GALSV type only existed in liquorice plants with high content of glycyrrhizic acid. HMGR gene sequences of G. uralensis are highly polymorphic and related to the content of glycyrrhizic acid.

  14. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

    PubMed

    Li, Yan-yan

    2012-01-01

    The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

  15. Plasminogen Activator Inhibitor-1 4G/5G Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis

    PubMed Central

    Li, Yan-yan

    2012-01-01

    Background The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. Objective and Methods The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. Results The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). Conclusions In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD. PMID:22496752

  16. Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies.

    PubMed

    Liang, Si-Qiao; Chen, Xiao-Li; Deng, Jing-Min; Wei, Xuan; Gong, Chen; Chen, Zhang-Rong; Wang, Zhi-Bo

    2014-01-01

    A number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case-control studies was thus performed. A literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations. Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179-2.609, I2 = 16.9%, studies  = 2, case  = 314, control  = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417-0.769, I2 = 0.0%, studies  = 11, case  = 1693, control  =  502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%, studies  = 11, case  = 1693, control  = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case  = 3160, control  = 3433). None of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population.

  17. A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn's disease and ulcerative colitis.

    PubMed

    Li, Peng; Yang, Xiao-Ke; Wang, Xiu; Zhao, Meng-Qin; Zhang, Chao; Tao, Sha-Sha; Zhao, Wei; Huang, Qing; Li, Lian-Ju; Pan, Hai-Feng; Ye, Dong-Qing

    2016-10-01

    Both Crohn's disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk. The PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. A total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR=0.88, 95% CI=0.82∼0.95, P=0.001; OR=0.82, 95% CI=0.76∼0.89, P<0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR=0.85, 95% CI=0.79∼0.91, P<0.001; OR=0.88, 95% CI=0.83∼0.93, P<0.001), but not with CD susceptibility in Caucasians. This meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  18. Identification of a polymorphic mucin-like gene expressed in the midgut of the mosquito, Aedes aegypti, using an integrated bulked segregant and differential display analysis.

    PubMed Central

    Morlais, I; Severson, D W

    2001-01-01

    The identification of putative differentially expressed genes within genome regions containing QTL determining susceptibility of the mosquito, Aedes aegypti, to the malarial parasite, Plasmodium gallinaceum, was investigated using an integrated, targeted approach based on bulked segregant and differential display analysis. A mosquito F2 population was obtained from pairwise matings between the parasite-susceptible RED strain and the resistant MOYO-R substrain. DNA from female carcasses was used to genotype individuals at RFLP markers of known chromosomal position around the major QTL (pgs 1). Midguts, dissected 48 hr after an infected blood meal, were used to prepare two RNA bulks, each representing one of the parental genotypes at the QTL interval. The RNA bulks were compared by differential display PCR. A mucin-like protein gene (AeIMUC1) was isolated and characterized. The gene maps within the pgs 1 QTL interval and is expressed in the adult female midgut. AeIMUC1 RNA abundance decreased with time after blood meal ingestion. No differential expression was observed between the two mosquito strains but three different alleles with inter- and intrastrain allelic polymorphisms including indels and SNPs were characterized. The AeIMUC1 gene chromosome location and allelic polymorphisms raise the possibility that the protein might be involved in parasite-mosquito interactions. PMID:11454761

  19. The association of two polymorphisms in adiponectin-encoding gene with hypertension risk and the changes of circulating adiponectin and blood pressure: A meta-analysis.

    PubMed

    Wu, Jianmin; Xu, Guoyan; Cai, Wenqin; Huang, Yun; Xie, Ningyu; Shen, Yihua; Xie, Liangdi

    2017-02-28

    This meta-analysis was prepared to synthesize published data on the association of two polymorphisms (T45G and G276T) in adiponectin-encoding gene (ADIPOQ) with hypertension risk and the changes of circulating adiponectin and blood pressure. Methodology and Major Findings: Data were collected and corrected by two authors, and were managed with Stata software. In total, 12 articles were synthesized, including 12 studies (3358 cases and 5121 controls) for the association of two study polymorphisms with hypertension risk and 11 studies (3053 subjects) for the between-genotype changes of adiponectin and/or blood pressure. Based on all qualified studies, the risk prediction for hypertension was nonsignificant for both polymorphisms, with significant heterogeneity for G276T polymorphism (I2 = 53.8%). Overall changes in adiponectin and blood pressure were also nonsignificant for T45G, while contrastingly 276GT genotype was associated with significantly higher levels of adiponectin (weighted mean difference [WMD] = 0.72 μg/mL, 95% confidence interval [CI]: 0.04 to 1.41, P = 0.038), systolic (WMD = 5.15 mm Hg, 95% CI: 0.98 to 9.32, P = 0.016) and diastolic (WMD = 3.45 mm Hg, 95% CI: 0.37 to 6.53, P = 0.028) blood pressure with evident heterogeneity (I2 = 72.0%, 78.3% and 80.0%, respectively), and these associations were more obvious in hypertensive patients. Publication bias was a low probability event for overall comparisons. Our findings suggested that in spite of the nonsignificant association between ADIPOQ T45G or G276T polymorphism and hypertension, the heterozygous mutation of G276T was observed to account for increased levels of circulating adiponectin and blood pressure, especially in hypertensive patients.

  20. Polymorphisms in DNA repair genes and associations with cancer risk.

    PubMed

    Goode, Ellen L; Ulrich, Cornelia M; Potter, John D

    2002-12-01

    Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.

  1. Investigation and analysis of single nucleotide polymorphisms in Janus kinase/signal transducer and activator of transcription genes with leukemia.

    PubMed

    Zhong, Yuejiao; Wu, Jianzhong; Chen, Baoan; Ma, Rong; Cao, Haixia; Wang, Zhuo; Cheng, Lu; Ding, Jiahua; Feng, Jifeng

    2012-06-01

    Aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may predispose to leukemia due to deregulation of proliferation, differentiation or apoptosis. This study was conducted to investigate whether any association exists between genetic polymorphisms in the JAK2, STAT3 and STAT5 genes and individual susceptibility to leukemia. A case-control study was carried out using a Chinese sample set with 344 cases of leukemia and 346 controls matched by age and ethnicity. Genomic DNA was assayed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) on 13 single nucleotide polymorphisms (SNPs). Genotype analyses showed that two SNPs, namely rs17886724 and rs2293157 located in STAT3 and STAT5, respectively, were significantly associated with leukemia (p < 0.05 for all). Interaction analyses of SNPs (rs17886724|rs2293157; rs11079041| rs2293157) showed that there were inferior associations in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) compared to the control group (0.1 > p > 0.05). Linkage disequilibrium existed between rs11079041 and rs2293157 in both leukemia and control groups (r(2) = 0.7). The haplotypes displayed significant association between rs11079041 and rs2293157 in both leukemia and control groups (p < 0.05). The accuracy rate of the support vector machine (SVM) classification model in making a prediction of leukemia was 97%. The results indicated that STAT3 and STAT5 gene SNPs may be prognostic of leukemia.

  2. The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals

    PubMed Central

    Young, Elizabeth H; Wareham, Nicholas J; Farooqi, Sadaf; Hinney, Anke; Hebebrand, Johannes; Scherag, André; O’Rahilly, Steve; Barroso, Inês; Sandhu, Manjinder S

    2009-01-01

    Background Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation. Methods We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8,304 individuals. We also did a meta-analysis of relevant studies, involving 10,975 cases and 18,588 controls, to place our findings in context. Finding In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% CI 4-30%, p=0·015) lower risk of obesity compared with noncarriers. There was no heterogeneity among studies and no apparent publication bias. Interpretation This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential. PMID:17356525

  3. Association Analysis of Two Single-Nucleotide Polymorphisms of the RELN Gene with Autism in the South African Population

    PubMed Central

    Sharma, Jyoti Rajan; Gameeldien, Hajirah; Davids, Muneera; Kaur, Mandeep; van der Merwe, Lize

    2013-01-01

    Background: Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. Aims: The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Methods: Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan® Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. Results: A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. Conclusion: There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population. PMID:23216241

  4. Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population.

    PubMed

    Sharma, Jyoti Rajan; Arieff, Zainunisha; Gameeldien, Hajirah; Davids, Muneera; Kaur, Mandeep; van der Merwe, Lize

    2013-02-01

    Autism (MIM209850) is a neurodevelopmental disorder characterized by a triad of impairments, namely impairment in social interaction, impaired communication skills, and restrictive and repetitive behavior. A number of family and twin studies have demonstrated that genetic factors play a pivotal role in the etiology of autistic disorder. Various reports of reduced levels of reelin protein in the brain and plasma in autistic patients highlighted the role of the reelin gene (RELN) in autism. There is no such published study on the South African (SA) population. The aim of the present study was to find the genetic association of intronic rs736707 and exonic rs362691 (single-nucleotide polymorphisms [SNPs] of the RELN gene) with autism in a SA population. Genomic DNA was isolated from cheek cell swabs from autistic (136) as well as control (208) subjects. The TaqMan(®) Real-Time polymerase chain reaction and genotyping assay was utilized to determine the genotypes. A significant association of SNP rs736707, but not for SNP rs362691, with autism in the SA population is observed. There might be a possible role of RELN in autism, especially for SA populations. The present study represents the first report on genetic association studies on the RELN gene in the SA population.

  5. [Meta-analysis of the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma gene with type 2 diabetes in Chinese Han population].

    PubMed

    Guo, Wu-Lan; Tang, Yong; Han, Xue-Yao; Ji, Li-Nong

    2011-12-01

    To evaluate the association of Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma (PPARgamma) gene with type 2 diabetes (T2DM) in Chinese Han population. The present investigation was carried out using the keywords "PPARgamma", "pparg", "Pro12Ala", "type 2 diabetes", and "Chinese. The odds ratios (OR) for Ala12 used as the metric of choice were calculated in the dominant and additive model separately. The Meta-analysis was conducted by software STATA 11.0. (1) We identified 22 studies, of which 17 studies involving 3927 type 2 diabetes cases and 3364 controls fell into the inclusion criteria. The analysis indicated no significant inter-study heterogeneity and publication bias. (2) The frequencies of the minor allele Ala12 in type 2 diabetes and control groups were 4.8% and 4.6% respectively. (3) The combined overall OR of dominant and additive model calculated by fix-effects meta-analysis for type 2 diabetes and the Pro12Ala polymorphism, were 0.95 (95% CI: 0.80, 1.12) and 0.93 (95% CI: 0.79, 1.09) respectively. In this meta-analysis, the Pro12Ala gene variant (rs1801282) is not found to be associated with the susceptibility for type 2 diabetes in Chinese Han population.

  6. Genetic analysis of the relationship between bone mineral density and low-density lipoprotein receptor-related protein 5 gene polymorphisms.

    PubMed

    Yi, Jiayong; Cai, Yu; Yao, Zhenjun; Lin, Jianping

    2013-01-01

    A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects. Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model. A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02 g/cm², 95% CI = 0.01-0.03, P < 10⁻⁴; at femur neck (FN): WMD = 0.01 g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02 g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02 g/cm², 95% CI = 0.02-0.03, P < 10⁻⁵; WMD at FN = 0.01 g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03 g/cm², 95% CI = 0.01-0.05, P = 0.005). This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.

  7. Genetic diversity analysis among male and female Jojoba genotypes employing gene targeted molecular markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) markers

    PubMed Central

    Heikrujam, Monika; Kumar, Jatin; Agrawal, Veena

    2015-01-01

    To detect genetic variations among different Simmondsia chinensis genotypes, two gene targeted markers, start codon targeted (SCoT) polymorphism and CAAT box-derived polymorphism (CBDP) were employed in terms of their informativeness and efficiency in analyzing genetic relationships among different genotypes. A total of 15 SCoT and 17 CBDP primers detected genetic polymorphism among 39 Jojoba genotypes (22 females and 17 males). Comparatively, CBDP markers proved to be more effective than SCoT markers in terms of percentage polymorphism as the former detecting an average of 53.4% and the latter as 49.4%. The Polymorphic information content (PIC) value and marker index (MI) of CBPD were 0.43 and 1.10, respectively which were higher than those of SCoT where the respective values of PIC and MI were 0.38 and 1.09. While comparing male and female genotype populations, the former showed higher variation in respect of polymorphic percentage and PIC, MI and Rp values over female populations. Nei's diversity (h) and Shannon index (I) were calculated for each genotype and found that the genotype “MS F” (in both markers) was highly diverse and genotypes “Q104 F” (SCoT) and “82–18 F” (CBDP) were least diverse among the female genotype populations. Among male genotypes, “32 M” (CBDP) and “MS M” (SCoT) revealed highest h and I values while “58-5 M” (both markers) was the least diverse. Jaccard's similarity co-efficient of SCoT markers ranged from 0.733 to 0.922 in female genotypes and 0.941 to 0.746 in male genotype population. Likewise, CBDP data analysis also revealed similarity ranging from 0.751 to 0.958 within female genotypes and 0.754 to 0.976 within male genotype populations thereby, indicating genetically diverse Jojoba population. Employing the NTSYS (Numerical taxonomy and multivariate analysis system) Version 2.1 software, both the markers generated dendrograms which revealed that all the Jojoba genotypes were clustered into two major groups

  8. Association between angiotensin converting enzyme gene insertion/deletion polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise meta-analysis

    PubMed Central

    Ai, Jin-Wei; Zeng, Xian-Tao; Liu, Ying; Fu, Yu; Liu, Tong-Zu; Pei, Bin

    2016-01-01

    Vesicoureteral reflex(VUR) is a common disease in children. Some studies indicated that the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism associated with the renal scar in VUR, but not all researchers agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM, and Embase databases were searched for studies that examined the relationship between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata 12.0 software was used for statistical analyses. 11 case-control studies with 1,032 VUR patients were analyzed. The results showed that the DD genotype and D allele were associated with renal scar risk in overall VUR patients, DD vs. DI + II: OR = 1.61, 95% CI = 1.04–2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20–2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02–1.86, P = 0.04. Similar results were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis indicated that the ACE DD genotype may increase the risk of renal scar in children with VUR. PMID:27506878

  9. Positive association between CD44 gene rs13347 C>T polymorphism and risk of cancer in Asians: a systemic review and meta-analysis

    PubMed Central

    Shi, Jinan; Duan, Yin; Pan, Lei; Zhou, Xiaoxi

    2016-01-01

    Background Cluster of differentiation 44 (CD44) is an important surface marker of cancer stem cells in a variety of tumors. A number of previous studies have been conducted to investigate the association between CD44 gene rs13347 C>T polymorphism and cancer risk in humans; nevertheless, the results remain controversial. We therefore performed this meta-analysis to confirm the role of this polymorphism in susceptibility to human cancer. Materials and methods The studies published up to December 2015 were searched in PubMed, Web of Science, and China National Knowledge Infrastructure databases. Twelve eligible case–control studies were identified, involving a total of 6,982 cases and 7,430 controls. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using a fixed or random-effect model to estimate the strength of the association. Results The results of the overall analyses indicated that CD44 gene rs13347 polymorphism was significantly associated with cancer risk in Asians (CT vs CC: OR =1.35, 95% CI =1.12–1.62; TT vs CC: OR =1.99, 95% CI =1.52–2.60; TT + CT vs CC: OR =1.41, 95% CI =1.16–1.71; and TT vs CC + CT: OR =1.74, 95% CI =1.41–2.14), especially in Chinese population (CT vs CC: OR =1.42, 95% CI =1.16–1.75; TT vs CC: OR =2.13, 95% CI =1.58–2.86; TT + CT vs CC: OR =1.50, 95% CI =1.21–1.87; and TT vs CC + CT: OR =1.80, 95% CI =1.43–2.26). In stratified analyses by cancer types, there was evidence for an association between this polymorphism and nasopharyngeal cancer and breast cancer, respectively. Conclusion The results of this meta-analysis suggest that the CD44 gene rs13347 C>T polymorphism is associated with elevated risk of human cancer in Asians, especially in Chinese population. Further well-designed studies on a larger population covering other ethnicities should be carried out to validate our results. PMID:27366086

  10. Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta-analysis.

    PubMed

    Clarke, Toni-Kim; Bloch, Paul J; Ambrose-Lanci, Lisa M; Ferraro, Thomas N; Berrettini, Wade H; Kampman, Kyle M; Dackis, Charles A; Pettinati, Helen M; O'Brien, Charles P; Oslin, David W; Lohoff, Falk W

    2013-07-01

    Genetic research on cocaine dependence (CD) may help clarify our understanding of the disorder as well as provide insights for effective treatment. As endocannabinoid signaling and dopamine neurotransmission have been shown to be involved in drug reward, genes related to these systems are plausible candidates for susceptibility to CD. The cannabinoid receptor 1 protein regulates both the endocannabinoid and dopaminergic neurobiological systems, and polymorphisms in the cannabinoid receptor gene, CNR1, have been associated previously with substance dependence. In this study, we attempt to replicate findings associating CNR1 with CD in African Americans. Cocaine-addicted individuals (n=860) and unaffected controls (n=334) of African descent were genotyped for two single nucleotide polymorphisms (SNPs) in CNR1 (rs6454674, rs806368). We observed a significant difference in genotype frequencies between cases and controls for both SNPs (P≤0.042). A meta-analysis was also performed combining our data with that of Zuo et al. who also studied these polymorphisms in African American cocaine addicts (total n=1253 cases versus 543 controls). When our data were combined, rs6454674 increased in significance to P=0.027; however, rs806368 was no longer significant. This study confirms the association between rs6454674 and CD. However, because there is considerable co-morbidity of CD with other drugs of abuse, additional studies are necessary to determine whether polymorphisms in CNR1 induce a general susceptibility to substance dependence or are specific to cocaine addiction. Furthermore, as this population consists of American individuals of African descent, the possibility of population stratification should not be excluded.

  11. Tumor necrosis factor-α gene polymorphisms and risk of oral cancer: evidence from a meta-analysis.

    PubMed

    Chen, Fang-Chun; Zhang, Fan; Zhang, Zhi-Jiao; Meng, Si-Ying; Wang, Yang; Xiang, Xue-Rong; Wang, Chun; Tang, Yu-Ying

    2013-01-01

    Numerous studies have been conducted regarding association between TNF-α and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-α-308G>A and four also concerned the TNF-α-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-α-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-α-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-α polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-α- 308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-α-238G>A may cause an increase.

  12. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects

    PubMed Central

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease. PMID:26885185

  13. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects.

    PubMed

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

  14. Relationship between TBX20 gene polymorphism and congenital heart disease.

    PubMed

    Yang, X F; Zhang, Y F; Zhao, C F; Liu, M M; Si, J P; Fang, Y F; Xing, W W; Wang, F L

    2016-06-02

    Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.

  15. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

    SciTech Connect

    Dong, Lihua; Cui, Jingkun; Tang, Fengjiao; Cong, Xiaofeng; Han, Fujun

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  16. Vitiligo susceptibility and catalase gene (CAT) polymorphisms in sicilian population.

    PubMed

    Caputo, Valentina; Niceta, Marcello; Fiorella, Santi; La Vecchia, Marco; Bastonini, Emanuela; Bongiorno, Maria R; Pistone, Giuseppe

    2017-02-15

    Catalase gene (CAT) polymorphisms were analyzed as responsible for the deficiency of catalase enzyme activity and concomitant accumulation of excessive hydrogen peroxide in Vitiligo patients. Catalase is a well known oxidative stress regulator that could play an important role in the pathogenesis of Vitiligo. This study was conducted to evaluate three CAT gene polymorphisms (-89A/T, 389C/T, 419C/T) and their association with Vitiligo susceptibility in Sicilian population. 60 out of 73 Sicilian patients with Vitiligo were enrolled and submitted to CAT gene analysis. Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT -89 T/T frequency was found to be significantly higher amongst Vitiligo patients than controls. Despite the involvement of the CAT enzyme in the pathogenesis of Vitiligo, the biological significance of CAT gene polymorphisms is still controversial. With the only exception for CAT variant -89A/T, the other studied CAT gene polymorphisms (389C/T and 419C/T) might not to be associated with Vitiligo in Sicilian population.

  17. Gene analysis using mass spectrometric cleaved amplified polymorphic sequence (MS-CAPS) with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF).

    PubMed

    Kajiwara, Hideyuki

    2015-01-01

    Mass spectrometric cleaved amplified polymorphic sequence (MS-CAPS) is a method for detecting genes using a combination of short PCR and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). MS-CAPS can identify a single nucleotide polymorphism (SNP) in less than one hour and is suitable for plants, animals, bacteria, and food.

  18. A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects.

    PubMed

    Zhou, Hua-Fu; Feng, Xu; Zheng, Bao-Shi; Qian, Jun; He, Wei

    2013-10-01

    The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04-1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23-1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.

  19. Analysis of single nucleotide polymorphisms in the SFRS3 and FKBP4 genes in corticosteroid-induced ocular hypertension.

    PubMed

    Hogewind, Barend F; Micheal, Shazia; Bakker, Bjorn; Hoyng, Carel B; den Hollander, Anneke I

    2012-12-01

    The use of intravitreal triamcinolone acetonide (IVTA) can cause ocular hypertension. This steroid response appears to be heritable and alleles in the SFRS3 and FKBP4 genes have recently been suggested to play a role. The purpose of the present study was to perform an independent replication study to determine whether single nucleotide polymorphisms (SNPs) in SFRS3 and FKBP4 are involved in the steroid response. A retrospective case-control study of native Dutch patients was performed who were treated with 4.0mg IVTA. The patients were divided into an intraocular hypertension group (intraocular pressure > 21 mmHg within a year after IVTA) and a non-intraocular hypertension group. The cohort was genotyped for three SNPs: rs7759778 and rs1406945 in SFRS3, and rs2968909 in FKBP4. A total of 102 patients was included: 58 steroid responders and 44 non-responders. No significant differences in demographic parameters or medical history were observed between the study groups. None of the SNPs were found to be significantly associated with the disease as no difference was revealed either in the genotype or allele frequencies between responders and non-responders. This study does not confirm a role for genetic variants in the SFRS3 and FKBP4 genes in the pathogenesis of corticosteroid-induced ocular hypertension. However, our limited sample size may have restricted the power of our study, and we therefore cannot exclude the involvement of these genetic variants in steroid response.

  20. Analysis of the association between interleukin-1beta (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population.

    PubMed

    Kaarthikeyan, Gurumoorthy; Jayakumar, Nadathur Doraisamy; Padmalatha, Ogoti; Sheeja, Varghese; Sankari, Malaippan; Anandan, Balakrisnan

    2009-01-01

    The aim of this study was to determine the association between IL-1B (+3954) gene polymorphism and chronic periodontitis in a sample of the south Indian population. This study employed a cross-sectional design involving individuals from the state of Tamil Nadu in the southern part of India. Genomic DNA was obtained from the white blood cells of 30 patients with chronic periodontitis (18 males and 12 females) and 31 healthy controls (20 males and 11 females). The age of the subjects ranged from 30 to 55 years old and all were non smokers. DNA was amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL-1beta gene and analyzed by 3% agarose gel electrophoresis. A Chi-square test was used to determine the genotype distribution between the groups and the relative risk was estimated with a 95% confidence interval. The chronic periodontitis group displayed a higher percentage of T allele, even though it was not statistically significant. The relative risk analysis between genotypes showed that the risk was higher for the CT genotype compared with the CC genotype and the risk was significant. In conclusion, our data suggested that there was no significant association between IL-1beta (+3954) gene polymorphism and chronic periodontitis in the south Indian population.

  1. [Analysis of gene polymorphism of HPA and HLA-I in Chinese Xi'an voluntary platelet donors].

    PubMed

    Wang, Xiao-Fang; Liu, Meng-Li; Zhou, Dang-Xia; Qi, Jun; Liu, Sheng; Wang, Tian-Ju

    2011-12-01

    To study the allele frequencies and their polymorphism characteristics of human platelet antigen (HPA) and human leucocyte antigen-I (HLA-I) in Chinese xi'an population, the types of HPA and HLA-I in 375 Chinese xi'an voluntary platelet donors were detected by PCR-SSP and PCR-SSO as well as flow cytometry with magnetic beads, and were analyzed. The results showed that there was no polymorphism in HPA-7-HPA-14, HPA-16 and HPA-17 which only expressed-aa type, the -bb type was only detected in HPA-3 and HPA-15, 9 out of 16 samples for the HPA-5ab phenotype simultaneously expressed HPA-15ab, the other 7 samples expressed HPA-15bb, no HPA-15aa phenotype was observed. Phenotypes detected in this study were HPA-1aa-17aa, HPA-1ab, -2ab, -3ab, -3bb, -4ab, -5ab, -6ab, -15ab and -15bb. Among 375 cases, HLA-A specificity of 16 species was observed, which accounted for 76% (16/21) of detectable phenotype specificity in this locus, moreover, 11 species showed frequency > 1%; HLA-B specificity of 36 species was observed which accounted for 84% (36/43) of detectable phenotype specificity in this locus, moreover 23 species showed frequency > 1%, these species were covered by common specific HLA-I in northern China, 264 species haplotype HLA-A-B were found in 375 cases, the frequency of 30 species was > 1%. It is concluded that the gene frequency distribution of HPA and HLA-I in Chinese Xi'an population is in accordance with population of northern China on the whole, but it has its own characteristics.

  2. APOE gene polymorphisms and diabetic peripheral neuropathy.

    PubMed

    Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-09-08

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

  3. G894T and 4a/b polymorphisms of NOS3 gene are not associated with cancer risk: a meta-analysis.

    PubMed

    Haque, Shafiul; Mandal, Raju K; Akhter, Naseem; Panda, Aditya K; Hussain, Arif; Khan, Saif; Lohani, Mohtashim

    2015-01-01

    Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and genetic polymorphisms of NOS3 gene play significant roles in various processes of carcinogenesis. The results from published studies on the association between NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflicting and inconclusive. However, i n order to assess this relationship more precisely, a meta-analysis was performed with PubMed (Medline), EMBASE and Google web searches until February 2014 to select all published case- control and cohort studies. Genotype distribution data were collected to calculate the pooled odd ratios (ORs) and 95% confidence intervals (CIs) to evaluate the strength of association. A total of 10,546 cancer cases and 10,550 controls were included from twenty four case-control studies for the NOS3 G894T polymorphism. The results indicated no significant association with cancer risk as observed in allelic (T vs G: OR=1.024, 95%CI=0.954 to 1.099, p=0.508), homozygous (TT vs GG: OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vs GG: OR=0.993, 95%CI=0.932 to 1.059, p=0.835), recessive (TT vs GG+GT: OR=1.100, 95%CI=0.936 to 1.293, p=0.249) and dominant (TT+GT vs GG: OR=1.012, 95%CI=0.927 to 1.105, p=0.789) genetic models. Similarly, a total of 3,449 cancer cases and 3,691 controls were recruited from fourteen case-control studies for NOS3 4a/b polymorphism. Pooled results indicated no significant association under allelic (A vs B: OR=0.981, 95%CI=0.725 to 1.329, p=0.902), homozygous (AA vs BB: OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vs BB: OR=1.129, 95%CI=0.896 to 1.422, p=0.305), dominant (AA+BA vs BB: OR=1.046, 95%CI=0.779 to 1.405, p=0.763) and recessive (AA vs BB+BA: OR=1.196, 95%CI=0.587 to 2.439, p=0.622) genetic contrast models. This meta-analysis suggests that G894T and 4a/b polymorphisms of NOS3 gene are not associated with increased or decreased risk of overall cancer.

  4. Innate Immune Gene Polymorphisms in Tuberculosis

    PubMed Central

    Sadee, Wolfgang

    2012-01-01

    Tuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB. PMID:22825450

  5. Replication and Meta-analysis of the Gene-Environment Interaction between Body Mass Index and the Interleukin-6 Promoter Polymorphism with Higher Insulin Resistance

    PubMed Central

    Underwood, Patricia C.; Chamarthi, Bindu; Williams, Jonathan S.; Sun, Bei; Vaidya, Anand; Raby, Benjamin A.; Lasky-Su, Jessica; Hopkins, Paul N.; Adler, Gail K.; Williams, Gordon H.

    2012-01-01

    Objective Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the Interleukin-6 (IL-6) gene that influences both IR and onset of type 2 diabetes mellitus (T2DM) with obese individuals homozygous for the C allele demonstrating the highest level of IR and greatest risk for T2DM. Replication of a gene-environment interaction is important to confirm the validity of the initial finding and extends the generalizability of the results to other populations. Thus, the objective of this study was to replicate this gene-environment interaction on IR in a hypertensive population and perform a meta-analysis with prior published results. Material and Methods The replication analysis was performed using Caucasian individuals with hypertension (HTN) from the HyperPATH cohort (N=311), genotyped for rs1800795. Phenotype studies were conducted after participants consumed two diets: high sodium (HS) (200mmol/day) and low sodium (LS) (10mmol/day) for 7 days each. Measurements for plasma glucose, insulin, and IL-6 were obtained after 8 hours of fasting. IR was characterized by the homeostatic model assessment (HOMA-IR). Results In HyperPATH, BMI was a significant effect modifier of the relationship between rs1800795 and HOMA-IR; higher BMI was associated with higher HOMA-IR among homozygote CC individuals when compared to major allele G carriers (p=0.003). Further, the meta-analysis in 1028 individuals confirmed the result demonstrating the same significant interaction between rs1800795 and BMI on HOMA-IR (p=1.05×10−6). Conclusion This rare replication of a gene-environment interaction extends the generalizability of the results to HTN while highlighting this polymorphism as a marker of IR in obese individuals. PMID:22075267

  6. Meta-analysis confirms a functional polymorphism (5-HTTLPR) in the serotonin transporter gene conferring risk of bipolar disorder in European populations.

    PubMed

    Jiang, Hong-Yan; Qiao, Fei; Xu, Xiu-Feng; Yang, Yuan; Bai, Yan; Jiang, Ling-Ling

    2013-08-09

    The serotonin transporter (5-HTT) is a candidate risk gene for bipolar disorder, and a functional polymorphism of 44-bp insertion/deletion (5-HTTLPR) located in the promoter region of this gene has been investigated for the association with the illness extensively among worldwide populations, but overall results were inconsistent and its role in the disorder remains unclear. The present study attempts to find its potential association with bipolar disorder using meta-analyzes that maximize the statistical power. We applied meta-analysis techniques by combining all available case-control studies of 5-HTTLPR and bipolar disorder in samples of European ancestry (with a total of 3778 cases and 4997 controls), and we assessed the evidence for allelic associations, heterogeneity among different studies, influence of each single study, and potential publication bias. The short allele (S allele) of 5-HTTLPR showed a significant association with bipolar disorder in our meta-analysis (odds ratio=1.10, p-value=0.005), suggesting it is likely a risk polymorphism for the illness, and the observed OR is consistent with other susceptibility loci identified through recent large-scale genetic association studies on bipolar disorder, which could be regarded simply as a small but detectable effects. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Identification of peptide-specific TCR genes by in vitro peptide stimulation and CDR3 length polymorphism analysis.

    PubMed

    Shao, Hongwei; Lin, Yanmei; Wang, Teng; Ou, Yusheng; Shen, Han; Tao, Changli; Wu, Fenglin; Zhang, Wenfeng; Bo, Huaben; Wang, Hui; Huang, Shulin

    2015-07-10

    Identification of TCR genes specific for tumor-associated antigens (TAAs) is necessary for TCR gene modification of T cells, which is applied in anti-tumor adoptive T cell therapy (ACT). The usual identification methods are based on isolating single peptide-responding T cells and cloning the TCR gene by in vitro expansion or by single-cell RT-PCR. However, the long and exacting in vitro culture period and demanding operational requirements restrict the application of these methods. Immunoscope is an effective tool that profiles a repertoire of TCRs and identifies significantly expanded clones through CDR3 length analysis. In this study, a survivin-derived mutant peptide optimized for HLA-A2 binding was selected to load DCs and activate T cells. The monoclonal expansion of TCRA and TCRB genes was separately identified by Immunoscope analysis and following sequence identification, the properly paired TCR genes were transferred into T cells. Peptide recognition and cytotoxicity assays indicated that TCR-modified PBMCs could respond to both the mutant and wild type peptides and lyse target cells. These results show that combining Immunoscope with in vitro peptide stimulation provides an alternative and superior method for identifying specific TCR genes, which represents a significant advance for the application of TCR gene-modified T cells.

  8. Relationship between -889 C/T polymorphism in interleukin-1A gene and risk of chronic periodontitis: Evidence from a meta-analysis with new published findings

    PubMed Central

    da Silva, Felipe-Rodolfo-Pereira; Guimarães-Vasconcelos, Any-Carolina-Cardoso; de-Carvalho-França, Luiz-Felipe; di-Lenardo, David; Rodrigues, Luana-Silva; Barreto-do-Nascimento, Maria-Luísa-Lima

    2017-01-01

    Background Periodontitis results from an inflammatory response caused by accumulative microorganisms in periodontal sites. Several factors are involved in pathogenesis of periodontitis, for example the -889 C/T polymorphism in interleukin-1A gene. This study aimed to evaluate the relationship between this polymorphism and risk of development of chronic periodontitis by a meta-analysis based in new published findings. Material and Methods Thereunto a review in literature was performed in the electronic biomedical and education databases (Cochrane Library, Google Scholar, MEDLINE and PubMed) to studies published before August 2, 2015, the abstracts were evaluated and the data extraction performed by two calibrated examiners. The calculations of the meta-analysis were obtained through statistical software Review Manager version 5.2 with calculation of Odds Ratio (OR), heterogeneity (I²) and Funnel plots with P <0.05. Results In overall, twenty-one case/control studies were selected with 2,174 patients with chronic periodontitis and 1, 756 controls. The meta-analysis showed T allele was associated with chronic periodontitis (OR = 1.22, 95% CI: 1.09, 1.36, P = 0.0004) with decreased value to heterogeneity (I² = 15%, P = 0.28). TT genotype was associated to patients with chronic periodontitis (OR = 1.40, 95% CI: 1.07, 1.83, P = 0.01). No publication bias was found in this meta-analysis by asymmetry in Funnel plots. Conclusions This meta-analysis with 2,174 patients with chronic periodontitis and 1, 756 controls evidenced the -889 C/T polymorphism is associated to risk of development of chronic periodontitis with no significant value to heterogeneity to allelic evaluation. Key words:Alleles, odds ratio, periodontal disease, cytokines. PMID:27918732

  9. Polymorphisms within inflammatory genes and colorectal cancer

    PubMed Central

    Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor

    2006-01-01

    Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130

  10. Polymorphisms in neuropeptide genes and bone mineral density in Korean postmenopausal women.

    PubMed

    Chun, Eun Hee; Kim, Hoon; Suh, Chang Suk; Kim, Jong Hak; Kim, Dong Yeon; Kim, Jung Gu

    2015-11-01

    The purpose of this study was to investigate the association between single nucleotide polymorphisms in neuropeptide genes and bone mineral density (BMD) in Korean postmenopausal women. Twenty polymorphisms in NMU (neuromedin U; two polymorphisms), NMU2R (NMU receptor 2; six polymorphisms), CART (cocaine- and amphetamine-regulated transcript; three polymorphisms), NPY (neuropeptide Y; four polymorphisms), NPY2R (NPY type 2 receptor; two polymorphisms), NOS1 (neuronal nitric oxide synthase; two polymorphisms), and MC4R (melanocortin 4 receptor; one polymorphism) genes were analyzed in 482 Korean postmenopausal women. BMD at the lumbar spine and femoral neck was also examined. Effects of polymorphisms on BMD were evaluated after adjusting for potential confounding factors using analysis of covariance. Odds ratios and 95% CIs for osteoporosis were estimated using χ2 test or Fisher's exact test. Among the polymorphisms measured, the AG genotype of CART rs2239670 had the highest BMD at the lumbar spine. Furthermore, osteoporosis at the lumbar spine was more frequently observed in the GG genotype of NPY rs17149106 polymorphism and in the CC genotype of NPY rs16123 polymorphism and was less frequently observed in the TT-TT genotype identified by a combined polymorphism in the NPY2R gene, compared with the other genotypes. The AA genotype of NOS1 rs1279104 polymorphism was found to have a 3.68-fold higher prevalence of osteoporosis at the femoral neck compared with the GG genotype (95% CI, 1.29-10.50; P = 0.02). Results suggest that CART rs2239670 polymorphism may be one of the genetic factors affecting lumbar spine BMD in Korean postmenopausal women and that NPY rs17149106, NPY rs16123, NOS1 rs1279104, and combined (rs2880415 and rs6857715) polymorphisms in the NPY2R gene may be useful in identifying women at risk for osteoporosis.

  11. Association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke in the Chinese population: a meta-analysis.

    PubMed

    Zhu, Xiao-Yan; Hou, Rong-Yao; Pan, Xu-Dong; Wang, Yu-Chun; Zhang, Zheng-Shou; Guo, Rui-You

    2015-01-01

    The association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke (IS) has been extensively studied; however, the results from genetic association studies have been inconsistent even in the Chinese population. As far as we know, there was no previous meta-analysis concerning this association in the Chinese population. Therefore, the aim of our meta-analysis was to further evaluate the association in the Chinese population. We collected all of the relevant studies from Pubmed, OVID, Embase, Chinese Wan Fang database, CNKI, Chongqing VIP database and CBM up to August 2014. The available data was analyzed by Stata (version 12.0). We used odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to present the strength of the association. Heterogeneity was evaluated by the Q-test and I(2) statistic. Different genetic models, subgroup analysis, publication bias and sensitivity analysis were used to improve the comprehensive understanding. The results showed a significant association between the MTHFR gene C677T polymorphism and IS in six genetic models (additive model: OR = 1.34, 95%CI: 1.17 ∼ 1.54, p < 0.001; dominant model: OR = 1.44, 95% CI:1.26 ∼ 1.64, p < 0.001; recessive model: OR = 1.45, 95% CI: 1.15 ∼ 1.83, p = 0.001; heterozygote model: OR = 1.35, 95% CI: 1.18 ∼ 1.55, p < 0.001; homozygote model: OR = 1.80, 95% CI: 1.34 ∼ 2.41, p < 0.001; and allelic model: OR = 1.34, 95% CI: 1.17 ∼ 1.53, p < 0.001) based on the overall population, as well as subgroup analysis. In addition, the similar results were obtained in the sensitivity analysis based on studies with the high quality. This meta-analysis presented a significant association between the MTHFR gene C677T polymorphism and IS, the T allele might be a risk factor for IS in the Chinese population.

  12. Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: Application for diagnosis, genetic counseling, and therapy

    SciTech Connect

    Hiort, O. Tufts-New England Medical Center, Boston, MA ); Huang, Q. ); Sinnecker, G.H.G.; Kruse, K. ); Sadeghi-Nejad, A.; Wolfe, H.J. ); Yandell, D.W. ) Harvard School of Public Health, Boston, MA )

    1993-07-01

    Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males. In this report, the authors address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families. DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied. Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing. Female family members were also studied to identify heterozygote carriers. Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions. One patient with incomplete androgen insensitivity was a mosaic for the mutation. Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child. The data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome. Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance. The identification of carriers is of substantial clinical importance for genetic counseling. 29 refs., 2 figs., 1 tab.

  13. Use of meta-analysis to combine candidate gene association studies: application to study the relationship between the ESR PvuII polymorphism and sow litter size

    PubMed Central

    Alfonso, Leopoldo

    2005-01-01

    This article investigates the application of meta-analysis on livestock candidate gene effects. The PvuII polymorphism of the ESR gene is used as an example. The association among ESR PvuII alleles with the number of piglets born alive and total born in the first (NBA1, TNB1) and later parities (NBA, TNB) is reviewed by conducting a meta-analysis of 15 published studies including 9329 sows. Under a fixed effects model, litter size values were significantly lower in the "AA" genotype groups when compared with "AB" and "BB" homozygotes. Under the random effects model, the results were similar although differences between "AA" and "AB" genotype groups were not clearly significant for NBA and TNB. Nevertheless, the most noticeable result was the high and significant heterogeneity estimated among studies. This heterogeneity could be assigned to error sampling, genotype by environment interaction, linkage or epistasis, as referred to in the literature, but also to the hypothesis of population admixture/stratification. It is concluded that meta-analysis can be considered as a helpful analytical tool to synthesise and discuss livestock candidate gene effects. The main difficulty found was the insufficient information on the standard errors of the estimated genotype effects in several publications. Consequently, the convenience of publishing the standard errors or the concrete P-values instead of the test significance level should be recommended to guarantee the quality of candidate gene effect meta-analyses. PMID:15943920

  14. Association of Reelin gene polymorphisms with autism.

    PubMed

    Serajee, Fatema J; Zhong, Hailang; Mahbubul Huq, A H M

    2006-01-01

    Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.

  15. Employment of single-strand conformation polymorphism analysis in screening for α-1,3 glucosyltransferase gene mutation A333V in Croatian population.

    PubMed

    Goreta, Sandra Supraha; Dabelic, Sanja; Dumic, Jerka

    2011-01-01

    Congenital disorder of glycosylation type Ic (CDG-Ic) is caused by mutations in hALG6 gene encoding α-1,3 glucosyltransferase (NP_037471.2), an enzyme that catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor in N-glycosylation process. The most frequent mutation in hALG6 gene causing CDG-Ic is c.998C>T that results in p.A333V substitution. Up-to-date, no CDG-Ic patient has been detected in Croatia. However, as a part of the comprehensive project undertaken with the aim to estimate the frequencies of the carriers for specific mutations and polymorphisms related to particular CDGs in Croatian population, we screened genomic DNA samples obtained from 600 healthy nonconsanguineous Croatian residents to determine the frequency of the A333V mutation. For that purpose, we established the conditions for polymerase chain reaction-based single-strand conformation polymorphism analysis that is suitable for primary screening and in population studies, especially when the initial sample volume is small or DNA quantity is limited. None of the analyzed samples carried this mutation, indicating that the frequency of the patients carrying this homozygous mutation in Croatian population would be <1 in 1.4×10(6).

  16. Sex Determination from Fragmented and Degenerated DNA by Amplified Product-Length Polymorphism Bidirectional SNP Analysis of Amelogenin and SRY Genes.

    PubMed

    Masuyama, Kotoka; Shojo, Hideki; Nakanishi, Hiroaki; Inokuchi, Shota; Adachi, Noboru

    2017-01-01

    Sex determination is important in archeology and anthropology for the study of past societies, cultures, and human activities. Sex determination is also one of the most important components of individual identification in criminal investigations. We developed a new method of sex determination by detecting a single-nucleotide polymorphism in the amelogenin gene using amplified product-length polymorphisms in combination with sex-determining region Y analysis. We particularly focused on the most common types of postmortem DNA damage in ancient and forensic samples: fragmentation and nucleotide modification resulting from deamination. Amplicon size was designed to be less than 60 bp to make the method more useful for analyzing degraded DNA samples. All DNA samples collected from eight Japanese individuals (four male, four female) were evaluated correctly using our method. The detection limit for accurate sex determination was determined to be 20 pg of DNA. We compared our new method with commercial short tandem repeat analysis kits using DNA samples artificially fragmented by ultraviolet irradiation. Our novel method was the most robust for highly fragmented DNA samples. To deal with allelic dropout resulting from deamination, we adopted "bidirectional analysis," which analyzed samples from both sense and antisense strands. This new method was applied to 14 Jomon individuals (3500-year-old bone samples) whose sex had been identified morphologically. We could correctly identify the sex of 11 out of 14 individuals. These results show that our method is reliable for the sex determination of highly degenerated samples.

  17. Sex Determination from Fragmented and Degenerated DNA by Amplified Product-Length Polymorphism Bidirectional SNP Analysis of Amelogenin and SRY Genes

    PubMed Central

    Masuyama, Kotoka; Shojo, Hideki; Nakanishi, Hiroaki; Inokuchi, Shota; Adachi, Noboru

    2017-01-01

    Sex determination is important in archeology and anthropology for the study of past societies, cultures, and human activities. Sex determination is also one of the most important components of individual identification in criminal investigations. We developed a new method of sex determination by detecting a single-nucleotide polymorphism in the amelogenin gene using amplified product-length polymorphisms in combination with sex-determining region Y analysis. We particularly focused on the most common types of postmortem DNA damage in ancient and forensic samples: fragmentation and nucleotide modification resulting from deamination. Amplicon size was designed to be less than 60 bp to make the method more useful for analyzing degraded DNA samples. All DNA samples collected from eight Japanese individuals (four male, four female) were evaluated correctly using our method. The detection limit for accurate sex determination was determined to be 20 pg of DNA. We compared our new method with commercial short tandem repeat analysis kits using DNA samples artificially fragmented by ultraviolet irradiation. Our novel method was the most robust for highly fragmented DNA samples. To deal with allelic dropout resulting from deamination, we adopted “bidirectional analysis,” which analyzed samples from both sense and antisense strands. This new method was applied to 14 Jomon individuals (3500-year-old bone samples) whose sex had been identified morphologically. We could correctly identify the sex of 11 out of 14 individuals. These results show that our method is reliable for the sex determination of highly degenerated samples. PMID:28052096

  18. Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis.

    PubMed Central

    Villard, E.; Tiret, L.; Visvikis, S.; Rakotovao, R.; Cambien, F.; Soubrier, F.

    1996-01-01

    Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage desequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms could be divided into two groups: five polymorphisms in the 5' region and three in the coding sequence and the 3' UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5' group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT)2/3 polymorphism. The second QTL would have a frequency of approximately .20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. PMID:8651305

  19. DNA polymorphism analysis of Brucella lipopolysaccharide genes reveals marked differences in O-polysaccharide biosynthetic genes between smooth and rough Brucella species and novel species-specific markers

    PubMed Central

    2009-01-01

    Background The lipopolysaccharide is a major antigen and virulence factor of Brucella, an important bacterial pathogen. In smooth brucellae, lipopolysaccharide is made of lipid A-core oligosaccharide and N-formylperosamine O-polysaccharide. B. ovis and B. canis (rough species) lack the O-polysaccharide. Results The polymorphism of O-polysaccharide genes wbkE, manAO-Ag, manBO-Ag, manCO-Ag, wbkF and wbkD) and wbo (wboA and wboB), and core genes manBcore and wa** was analyzed. Although most genes were highly conserved, species- and biovar-specific restriction patterns were found. There were no significant differences in putative N-formylperosamyl transferase genes, suggesting that Brucella A and M serotypes are not related to specific genes. In B. pinnipedialis and B. ceti (both smooth), manBO-Ag carried an IS711, confirming its dispensability for perosamine synthesis. Significant differences between smooth and rough species were found in wbkF and wbkD, two adjacent genes putatively related to bactoprenol priming for O-polysaccharide polymerization. B. ovis wbkF carried a frame-shift and B. canis had a long deletion partially encompassing both genes. In smooth brucellae, this region contains two direct repeats suggesting the deletion mechanism. Conclusion The results define species and biovar markers, confirm the dispensability of manBO-Ag for O-polysaccharide synthesis and contribute to explain the lipopolysaccharide structure of rough and smooth Brucella species. PMID:19439075

  20. Identification and Analysis of Informative Single Nucleotide Polymorphisms in 16S rRNA Gene Sequences of the Bacillus cereus Group

    PubMed Central

    Hakovirta, Janetta R.; Prezioso, Samantha; Hodge, David; Pillai, Segaran P.

    2016-01-01

    Analysis of 16S rRNA genes is important for phylogenetic classification of known and novel bacterial genera and species and for detection of uncultivable bacteria. PCR amplification of 16S rRNA genes with universal primers produces a mixture of amplicons from all rRNA operons in the genome, and the sequence data generally yield a consensus sequence. Here we describe valuable data that are missing from consensus sequences, variable effects on sequence data generated from nonidentical 16S rRNA amplicons, and the appearance of data displayed by different software programs. These effects are illustrated by analysis of 16S rRNA genes from 50 strains of the Bacillus cereus group, i.e., Bacillus anthracis, Bacillus cereus, Bacillus mycoides, and Bacillus thuringiensis. These species have 11 to 14 rRNA operons, and sequence variability occurs among the multiple 16S rRNA genes. A single nucleotide polymorphism (SNP) previously reported to be specific to B. anthracis was detected in some B. cereus strains. However, a different SNP, at position 1139, was identified as being specific to B. anthracis, which is a biothreat agent with high mortality rates. Compared with visual analysis of the electropherograms, basecaller software frequently missed gene sequence variations or could not identify variant bases due to overlapping basecalls. Accurate detection of 16S rRNA gene sequences that include intragenomic variations can improve discrimination among closely related species, improve the utility of 16S rRNA databases, and facilitate rapid bacterial identification by targeted DNA sequence analysis or by whole-genome sequencing performed by clinical or reference laboratories. PMID:27582514

  1. Identification and Analysis of Informative Single Nucleotide Polymorphisms in 16S rRNA Gene Sequences of the Bacillus cereus Group.

    PubMed

    Hakovirta, Janetta R; Prezioso, Samantha; Hodge, David; Pillai, Segaran P; Weigel, Linda M

    2016-11-01

    Analysis of 16S rRNA genes is important for phylogenetic classification of known and novel bacterial genera and species and for detection of uncultivable bacteria. PCR amplification of 16S rRNA genes with universal primers produces a mixture of amplicons from all rRNA operons in the genome, and the sequence data generally yield a consensus sequence. Here we describe valuable data that are missing from consensus sequences, variable effects on sequence data generated from nonidentical 16S rRNA amplicons, and the appearance of data displayed by different software programs. These effects are illustrated by analysis of 16S rRNA genes from 50 strains of the Bacillus cereus group, i.e., Bacillus anthracis, Bacillus cereus, Bacillus mycoides, and Bacillus thuringiensis These species have 11 to 14 rRNA operons, and sequence variability occurs among the multiple 16S rRNA genes. A single nucleotide polymorphism (SNP) previously reported to be specific to B. anthracis was detected in some B. cereus strains. However, a different SNP, at position 1139, was identified as being specific to B. anthracis, which is a biothreat agent with high mortality rates. Compared with visual analysis of the electropherograms, basecaller software frequently missed gene sequence variations or could not identify variant bases due to overlapping basecalls. Accurate detection of 16S rRNA gene sequences that include intragenomic variations can improve discrimination among closely related species, improve the utility of 16S rRNA databases, and facilitate rapid bacterial identification by targeted DNA sequence analysis or by whole-genome sequencing performed by clinical or reference laboratories. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Association Between the Interleukin-10-1082G/A, -592C/A, -819C/T Gene Polymorphism and HIV-1 Susceptibility: A Meta-Analysis.

    PubMed

    Jiang, Caixiao; Liu, Shujun; Liu, Shuxia; Li, Zhanzhan; Chen, Peng; Chen, Lizhang

    2017-01-01

    . AA model: OR = 1.63, 95% CI = 1.11-2.38, p = .012; AG vs. AA model: OR = 1.32, 95% CI = 0.95-1.84, p = .094; GG+AA vs. AG model: OR = 0.92, 95% CI = 0.72-1.19, p = .537). In general, the meta-analysis found no marked association between the IL-10-1082G/A gene polymorphism and HIV-1 susceptibility, IL-10-529C/A gene polymorphism might lead to a decreased risk of HIV-1 infection, and IL-10-819C/T gene polymorphism might lead to an increased risk of HIV-1 infection.

  3. NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review

    PubMed Central

    Berardinelli, Francesco; di Masi, Alessandra; Antoccia, Antonio

    2013-01-01

    The relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim of this review is to provide the reader with the state of the art on the association between common genetic variants and cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated E185Q NBN miscoding variant. PMID:24396275

  4. [Association between CDH23 gene polymorphisms and susceptibility to noise-induced hearing loss in the Chinese population: a meta-analysis].

    PubMed

    Yu, J N; Wu, S S; He, C H; Zhang, C Y; Mu, H X; Ma, W S; Liu, B; Zhang, Y; Yu, S F

    2016-12-20

    Objective: To investigate the association between cadherin-23 (CDH23) gene polymorphisms and susceptibility to noise-induced hearing loss (NIHL) in the Chinese population through a meta-analysis. Methods: In June 2016, CNKI, VIP, Wanfang Data, and PubMed were searched for studies on the association between CDH23 gene polymorphisms and susceptibility to NIHL in the Chinese population. The articles were screened according to inclusion and exclusion criteria and related data were extracted. RevMan 5.3 was used for the meta-analysis. Results: A total of three Chinese articles were included. For CDH23-rs1227049, the risk of NIHL in people with C allele was 0.82 times (95%CI 0.39-1.73) that in people with G allele, the risk of NIHL in people with CG+CC genotype in the dominant model was 0.70 times (95%CI 0.34-1.43) that in people with GG genotype, the risk of NIHL in people with CC genotype in the recessive model was 1.23 times (95%CI 0.28-5.43) that in people with CG+GG genotype, and the risk of NIHL in people with CC genotype in the additive model was 1.05 times (95%CI 0.20-5.44) that in people with GG genotype (all P>0.05) . For CDH23-rs1227051, the risk of NIHL in people with T allele was 0.98 times (95%CI 0.71-1.37) that in people with C allele, and the risk of NIHL in people with CT+CC genotype in the dominant model was 1.09 times (95%CI 0.75-1.57) that in patients with TT genotype (both P>0.05) . Conclusion: There is still no enough evidence for the determination of CDH23-rs1227049 and CDH23-rs1227051 to be the susceptibility gene loci of NIHL.

  5. Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis.

    PubMed

    Silva, J De Azevedo; Lima, S C; Addobbati, C; Moura, R; Brandão, L A Cavalcanti; Pancoto, J A Trés; Donadi, E A; Crovella, S; Sandrin-Garcia, P

    2016-10-24

    Systemic lupus erythematosus (SLE) is a complex autoimmune disorder presenting heterogeneous clinical manifestations. A number of genes involved in SLE susceptibility are related to the type I interferon (IFN) pathway. IFN mediates innate immune responses and its increased levels contribute to the breakdown of peripheral tolerance. Interferon-induced helicase C domain 1 (IFIH1) activates and modulates IFN responses through its caspase recruitment domain. In this study, we analyzed four IFIH1 single nucleotide polymorphisms (SNPs): rs6432714, rs10930046, rs1990760, and rs3747517, in 337 patients with SLE and 373 healthy individuals from southeast and northeast Brazil. Our results did not find an association between IFIH1 SNPs and SLE (P value >0.025 after Bonferroni's adjustment). However, meta-analysis of peer-reviewed articles from 2008 to 2015 and data from this study indicated an association between rs1990760 and SLE onset (P < 0.05). This is the first association analysis on IFIH1 polymorphisms and SLE susceptibility in Brazilian populations.

  6. A serotonin transporter gene (SLC6A4) polymorphism is associated with reduced risk of irritable bowel syndrome in American and Asian population: a meta-analysis.

    PubMed

    Areeshi, Mohammed Y; Haque, Shafiul; Panda, Aditya K; Mandal, Raju K

    2013-01-01

    Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility. Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population. This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.

  7. [Analysis of associations of polymorphic loci of a tumor suppressor gene TP53 with malignant neoplasms in glass fiber manufacturing workers].

    PubMed

    Mukhammadiyeva, G F; Bakirov, A B; Karimova, L K; Valeyeva, E T

    2014-01-01

    The purpose of the study was to determine the role of TP53 tumor suppressor gene polymorphisms in the occurrence of skin malignant neoplasms in glass fiber manufacturing workers. We carried out a comparative study of polymorphous loci Arg72Pro and dup16bp in TP53 gene in workers with skin cancer and hyperkeratosis (n = 68), occupied in continuous glass fiber manufacture, and in healthy workers (n = 52). The associations of both Pro and dup16 minor alleles of TP53 gene, and Arg/Pro-W/dup16 genotype combination with higher risks for skin oncologic diseases of occupational genesis have been revealed.

  8. Meta-Analysis on the Relationship between HLA-DRBl Gene Polymorphism and Cervical Cancer in Chinese Population

    PubMed Central

    Wei, Lin-zhen; Wang, Hai-lin; Liu, Xin; Lu, Ya-peng; Xu, Fei; Yuan, Jin-qiu; Ling, Ya-qin

    2014-01-01

    Aim To determine the association between HLA-DRB1 haplotypes and risk of cervical cancer in unselected and samples from Chinese ethnicities. Methods A comprehensive search for articles from their inception to April 1st, 2013 was conducted from PubMed, Medline, Elsevier Science, Springer Link, Cochrane Library database, China biology medical literature database (CBM),China National Knowledge Infrastructure (CNKI),VIP,and Chinese literature database(Wang fang). A total of 1596 patients with cervical cancer and 2048 controls from the 12 studies on the relationship between gene polymorphism of HLA-DRB l and cervical cancer were performed and data were analyzed and processed using Review Manager 5.0 and Stata 11.0. Results Among the 13 family alleles, two (DRB1*03 and DRB1*08) were found to be negatively associated with cervical cancer in all studies or in Uighur subgroups, and two (DRB1*10 and DRB1*15) were positively associated with in all studies or in Uighur subgroups. Among the 25 specific alleles, six (DRB1*0301, *0403,*0404, *0803, *1312 and *1502) were associated with an increased risk cervical cancer in all studies. No significant association was established for other HLA-DRB1 family alleles and specific alleles. Ethnicity partially explained the race influence of DRB1*12, DRB1*14, DRB1*0301, DRB1*0403, DRB1*0404, DRB1*0803, DRB1*1312 and DRB1*1502 phenotypes. Conclusion Our results support the hypothesis that the HLA-DRB1 family alleles and specific alleles might influence the susceptibility or resistance to cervical cancer, suggesting that immune regulation may play a key role in this disease, although further investigations are still needed. PMID:24551099

  9. The HLA genes and their diverse polymorphism.

    PubMed

    Mehra, N K

    2000-08-01

    Advanced DNA level studies based on HLA class II sequence analysis have revealed considerable diversity in HLA among Asian Indians. High resolution typing of specific alleles such as DR2 and DR4 in the HLA class II region by PCR-SSP or SSOP hybridization and their associated DR-DQ haplotypes have helped to detect unique haplotypes and novel alleles which have subsequently been confirmed by sequencing. Incidentally, remarkable stability has been maintained in several other DRB1 alleles viz. DR1, DR7, DR9 and DR10. The ARMS-PCR technology has been found to be particularly useful for typing HLA-A, HLA-B and HLA-Cw alleles. These technologies are far superior over serological methods. Our studies have shown remarkable heterogeneity of common HLA-A and B alleles in Asian Indians. Molecular subtyping of HLA-A2 revealed that subtype A(*)0211 is found only in Indian population and may be the result of selection pressure in this population. Investigations into polymorphism in the HLA-B27 gene revealed that subtypes common both to the western caucasians and orientals occur in the Indian population. It is apparent that the population of the Indian subcontinent, placed as it is between the Caucasoids and Negroids on one hand and Australoids and Mongoloids on the other, provides a rich source of many HLA haplotypes. While the most frequent Caucasian haplotypes occur with a reasonable frequency in Asian Indians, those found predominantly in other ethnic groups (e.g., australian Aborigines and populations of Oceania, China and Japan) are also detected. Knowledge on this is most important for donor selection during organ and bone marrow transplantation and for designing MHC targeted vaccines in specific diseases.

  10. Study of bovine gene: the temporal-spatial expression patterns, polymorphism and association analysis with meat production traits.

    PubMed

    Juszczuk-Kubiak, E; Bujko, K; Grześ, M; Cymer, M; Wicińska, K; Szostak, A; Pierzchała, M

    2016-11-01

    The gene () encodes a transcription factor belonging to the MEF2 family that plays an important role in myogenesis by transcriptional regulation of genes involved in skeletal muscle growth and development. Despite the established importance of the factors in the muscular growth and development, the temporal-spatial expression and biological function of have not been reported in cattle. The aim of this study was to analyze the level of expression in the developing longissimus dorsi muscle (LM) of 4 cattle breeds (Polish Holstein-Friesian [HF], Limousine [LIM], Hereford [HER], Polish Red [PR]), differing in terms of meat production and utility type, at 6, 9, and 12 mo of age. The genetic polymorphism and expression patterns in 6 tissues (heart, spleen, liver, semitendinosus muscle [ST], gluteus medius muscle [GM], and LM) were also investigated. The results showed that mRNA was expressed at a high level in adult skeletal and cardiac muscles. Moreover, expression was markedly greater in the GM than in the LM ( 0.05) and ST ( 0.01). An age-dependent and breed-specific comparison of mRNA level in skeletal muscle of HF, LIM, HER, and PR bulls showed that age was significant differentiating factor of transcript/protein abundance in the LM of HER and LIM ( 0.001) compared to HF and PR, for which the differences in mRNA level were not significant ( > 0.05). Regarding the breed effect on the expression, significantly greater mRNA/protein level was noticed in the LM of 9 and 12 mo-old HER than of LIM ( 0.01), HF ( 0.001), and PR ( 0.001). Four novel SNP, namely, (promoter), (exon 7), (exon 8), and (3'UTR), were identified. We found that 3'UTR variant, situated within the seed region of the miR-5187-3p and miR-6931-5p binding sites, was associated with the level of mRNA/protein in LM of 12-mo-old HF bulls. In addition, we observed a significant association between some carcass quality traits, including meat and carcass fatness quality traits, and various 3'UTR genotypes in the

  11. Association of single nucleotide polymorphisms in the CYP1B1 gene with the risk of primary open-angle glaucoma: a meta-analysis.

    PubMed

    Wang, Z; Li, M; Li, L; Sun, H; Lin, X Y

    2015-12-17

    Mutations in the CYP1B1 gene were detected in primary open-angle glaucoma (POAG) patients. However, the association between these mutations and the incidence of POAG remains to be elucidated. Here, we have conducted a meta-analysis to analyze this correlation, using relevant studies obtained from an extensive search of various electronic databases, including EMBase, Web of Science, and PubMed. The extracted studies were selected for the meta-analysis based on the inclusion and exclusion criteria. The quality of each included study was assessed by the Newcastle-Ottawa scale (NOS), and the I2 value was calculated to evaluate the heterogeneity between studies. The combined effect size was presented as the odds ratio (OR), and confidence intervals (CI) were used to assess the association between POAG and CYP1B1 mutations. Eight studies, each with a high NOS score, were included in the analysis. Compared to the mutant allele, the wild-type allele of the rs180040 polymorphism in POAG patients showed a 12% decrease in OR (OR = 0.88, 95%CI = 0.76- 1.00); also, the wild-type allele of rs1056827 showed a 23% decrease in OR of the incidence of POAG (OR = 0.77, 95%CI = 0.60-0.99). However, the latter result was controversial. Polymorphisms at rs1056836, rs10012, and rs1056837 were not correlated with the incidence of POAG (using any evaluation model). In conclusion, three of the tested SNPs in the CYP1B1 gene were correlated with POAG; however, the SNPs rs180040 and rs1056827 showed an association with risk of POAG. These results must be further validated with larger-scale evaluations.

  12. Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism and Vesicoureteral Reflux in Children: A Meta-Analysis of 14 Case-Control Studies.

    PubMed

    Ai, Jin-Wei; Liu, Yu; Zeng, Xian-Tao; Lei, Qing; Zou, Li; Pei, Bin

    2015-12-01

    Vesicoureteral reflux (VUR) is a common and serious urinary disease in children. It usually causes renal scar, urinary tract infection, and chronic renal failure. Previous studies showed the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism might be associated with VUR; however, the conclusions were inconsistent. Therefore we used the meta-analytic approach to clarify the effect of ACE I/D polymorphism on VUR risk.We systematically searched the PubMed, CNKI, and EMBASE databases to identify all the potentially related studies published up to February 4, 2015. Two reviewers independently selected studies and extracted data. The strength of the association was assessed using odd ratio (OR) with its 95% confidence interval (CI) based on fixed or random effects model. The STATA 12.0 software was used for data analysis.A total of 14 case-control studies involving 1197 VUR patients and 1320 healthy controls met the eligibility criteria. Results of meta-analysis showed significant association between ACE I/D polymorphism and VUR risk (D vs. I: OR = 1.28, 95% CI = 1.06-1.54, P = 0.01; DD vs. II: OR = 1.44, 95% CI = 1.12-1.85, P = 0.01; DD vs. DI + II: OR = 1.49, 95% CI = 1.23-1.79, P < 0.01; DD + DI vs. II: OR = 1.20, 95% CI = 0.84-1.72, P = 0.31). Subgroup analyses revealed varied results. In Turkish people, results of all the genetic models other than DI vs. II showed statistical significance; in Caucasians, DD vs. DI + II showed statistical significance; and in Asians, DI versus II showed statistical significance.Our meta-analysis indicated that the ACE I/D polymorphism might be associated with increased risk of VUR in children. However, due to the limitations, we suggest conducting additional studies with larger sample size and adjustment for various risk factors, in the future for further clarification.

  13. Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma

    PubMed Central

    Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

    2015-01-01

    Background: Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. Materials and methods: We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ2 test and genetic model analysis. Results: In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of “GCT” in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Conclusions: Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively. PMID:26328260

  14. Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

    PubMed Central

    McGee, Kate; Lancaster, Germaine; Gold, Bert; Dean, Michael

    2011-01-01

    Background ABCB5 is a member of the ABC protein superfamily, which includes the transporters ABCB1, ABCC1 and ABCG2 responsible for causing drug resistance in cancer patients and also several other transporters that have been linked to human disease. The ABCB5 full transporter (ABCB5.ts) is expressed in human testis and its functional significance is presently unknown. Another variant of this transporter, ABCB5 beta posses a “half-transporter-like” structure and is expressed in melanoma stem cells, normal melanocytes, and other types of pigment cells. ABCB5 beta has important clinical implications, as it may be involved with multidrug resistance in melanoma stem cells, allowing these stem cells to survive chemotherapeutic regimes. Methodology/Principal Findings We constructed and examined in detail topological structures of the human ABCB5 protein and determined in-silico the cSNPs (coding single nucleotide polymorphisms) that may affect its function. Evolutionary analysis of ABCB5 indicated that ABCB5, ABCB1, ABCB4, and ABCB11 share a common ancestor, which began duplicating early in the evolutionary history of chordates. This suggests that ABCB5 has evolved as a full transporter throughout its evolutionary history. Conclusions/Significance From our in-silco analysis of cSNPs we found that a large number of non-synonymous cSNPs map to important functional regions of the protein suggesting that these SNPs if present in human populations may play a role in diseases associated with ABCB5. From phylogenetic analyses, we have shown that ABCB5 evolved as a full transporter throughout its evolutionary history with an absence of any major shifts in selection between the various lineages suggesting that the function of ABCB5 has been maintained during mammalian evolution. This finding would suggest that ABCB5 beta may have evolved to play a specific role in human pigment cells and/or melanoma cells where it is predominantly expressed. PMID:21298007

  15. Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene.

    PubMed

    Soares, Vítor Yamashiro Rocha; Silva, Jailthon Carlos da; Silva, Kleverton Ribeiro da; Pires e Cruz, Maria do Socorro; Santos, Marcos Pérsio Dantas; Ribolla, Paulo Eduardo Martins; Alonso, Diego Peres; Coelho, Luiz Felipe Leomil; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery

    2014-06-01

    An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.

  16. Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene

    PubMed Central

    Soares, Vítor Yamashiro Rocha; da Silva, Jailthon Carlos; da Silva, Kleverton Ribeiro; Cruz, Maria do Socorro Pires e; Santos, Marcos Pérsio Dantas; Ribolla, Paulo Eduardo Martins; Alonso, Diego Peres; Coelho, Luiz Felipe Leomil; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery

    2014-01-01

    An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA. PMID:24821056

  17. The FTO Gene rs9939609 Polymorphism Predicts Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Liu, Chibo; Mou, Sihua; Pan, Chunqin

    2013-01-01

    Objective Genome-wide association studies have shown that variance in the fat mass- and obesity- associated gene (FTO) is associated with risk of obesity in Europeans and Asians. Since obesity is associated with an increased risk of cardiovascular disease (CVD), several studies have investigated the association between variant in the FTO gene and CVD risk, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of rs9939609 variant (or its proxies [r2>0.90]) in the FTO gene with CVD risk. Methods Published literature from PubMed and Embase was retrieved. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random- effects model. Results A total of 10 studies (comprising 19,153 CVD cases and 103,720 controls) were included in the meta-analysis. The results indicated that the rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18, 95% confidence interval = 1.07–1.30, p = 0.001 [Z test], I2 = 80.6%, p<0.001 [heterogeneity]), and there was an insignificant change after adjustment for body mass index (BMI) and other conventional CVD risk factors (odds ratio = 1.16, 95% confidence interval = 1.05–1.27, p = 0.003 [Z test], I2 = 75.4%, p<0.001 [heterogeneity]). Conclusions The present meta-analysis confirmed the significant association of the rs9939609 variant in the FTO gene with CVD risk, which was independent of BMI and other conventional CVD risk factors. PMID:23977173

  18. The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: a systematic review and meta-analysis.

    PubMed

    Liu, Chibo; Mou, Sihua; Pan, Chunqin

    2013-01-01

    Genome-wide association studies have shown that variance in the fat mass- and obesity- associated gene (FTO) is associated with risk of obesity in Europeans and Asians. Since obesity is associated with an increased risk of cardiovascular disease (CVD), several studies have investigated the association between variant in the FTO gene and CVD risk, with inconsistent results. In this study, we performed a meta-analysis to clarify the association of rs9939609 variant (or its proxies [r (2)>0.90]) in the FTO gene with CVD risk. Published literature from PubMed and Embase was retrieved. Pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random- effects model. A total of 10 studies (comprising 19,153 CVD cases and 103,720 controls) were included in the meta-analysis. The results indicated that the rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18, 95% confidence interval = 1.07-1.30, p = 0.001 [Z test], I (2) = 80.6%, p<0.001 [heterogeneity]), and there was an insignificant change after adjustment for body mass index (BMI) and other conventional CVD risk factors (odds ratio = 1.16, 95% confidence interval = 1.05-1.27, p = 0.003 [Z test], I (2) = 75.4%, p<0.001 [heterogeneity]). The present meta-analysis confirmed the significant association of the rs9939609 variant in the FTO gene with CVD risk, which was independent of BMI and other conventional CVD risk factors.

  19. Effects of paraoxonase 1 gene polymorphisms on heart diseases

    PubMed Central

    Hernández-Díaz, Yazmín; Tovilla-Zárate, Carlos Alfonso; Juárez-Rojop, Isela Esther; González-Castro, Thelma Beatriz; Rodríguez-Pérez, Candelario; López-Narváez, María Lilia; Rodríguez-Pérez, José Manuel; Cámara-Álvarez, José Francisco

    2016-01-01

    Abstract Background: Associations between paraoxonase 1 (PON1) gene polymorphisms and heart diseases (HD) risk remain inconsistent. In order to obtain address this issue we performed a meta-analysis to assess the association between the L55M and Q192R polymorphisms of PON1 gene and heart diseases risk. Methods: Relevant studies were enrolled by searching databases systematically. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. Subgroup analyses were conducted for diagnostic and ethnicity. The heterogeneity among each of the studies was calculated by using Cochran Qtest and the inconsistency index (I2), and Begg's funnel plot and Egger's tests were performed to evaluate publication bias. Result: Sixty four studies involving a total of 19,715 cases and 33,397 controls were included in this meta-analysis. We found that the L55M polymorphism showed a significant association with heart diseases in Europeans (OR 1.44, 95%CI 1.33–1.56) and Asians (OR 1.18, 95%CI 1.03–1.35). This meta-analysis also showed a protective association of Q192R polymorphism with HD in Asian (OR 0.49, 95%CI 0.37–0.66) and African populations (OR 0.67, 95%CI 0.53–0.84). The 192R allele significantly decreased the risk of myocardial infarction (OR 0.75, 95%CI 0.57–0.99) and coronary artery disease (OR 0.91, 95%CI 0.84–0.98); however, individuals with 192Q allele had a markedly increased risk of coronary artery disease development (OR 1.38, 95%CI 1.22–1.56). Conclusion: This study demonstrated that the genetic risk for heart diseases is associated with the PON1 gene polymorphisms. L55M polymorphism is a risk factor and Q192R polymorphism is protective in certain populations. It is worth noting that the 192Q allele may be a risk factor to develop coronary artery disease. PMID:27858903

  20. Association of fat-mass and obesity-associated gene FTO rs9939609 polymorphism with the risk of obesity among children and adolescents: a meta-analysis.

    PubMed

    Quan, L-L; Wang, H; Tian, Y; Mu, X; Zhang, Y; Tao, K

    2015-02-01

    To elucidate the association of fat-mass and obesity-associated gene (FTO) rs9939609 polymorphism with obesity among children and adolescents. A literature search was conducted in PubMed, MEDLINE, Springer, and Google scholar to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used for four models: co-dominant model (AA vs. TT, AT vs. TT), dominant model (AA + AT vs. TT), recessive model (AA vs. AT + TT), and allelic model (A vs. T). Subgroup analyses stratified by ethnicity (Caucasian, others) and participants (children, children and adolescents) were assessed under allelic model. The heterogeneity and publication bias were examined. This meta-analysis included 12 eligible studies consisting 5,000 cases and 9,853 controls. The results revealed that FTO rs9939609 polymorphism was significantly associated with the increased risk of obesity in co-dominant model (AA vs. TT: OR = 1.91, 95% CI: 1.47-2.48, p < 0.01; AT vs. TT: OR = 1.18, 95% CI: 1.02-1.38, p = 0.03), dominant model (AA + AT vs. TT: OR = 1.47, 95% CI: 1.35-1.59, p < 0.01), recessive model (AA vs. AT + TT: OR = 1.79, 95% CI: 1.47-2.17, p < 0.01), and allelic model (A vs. T: OR = 1.39, 95% CI: 1.22-1.58, p < 0.01). Similar results were obtained for the subgroup analyses stratified by ethnicity and participants under allelic model. FTO rs9939609 polymorphism is associated with the increased risk of obesity among children and adolescents, especially the homozygous carriers.

  1. Polymerase chain reaction-restriction fragment length polymorphism analysis of a 16S rRNA gene fragment for authentication of four clam species.

    PubMed

    Fernandez, Alicia; García, Teresa; Gonzalez, Isabel; Asensio, Luis; Rodriguez, Miguel Angel; Hernández, Pablo E; Martin, Rosario

    2002-04-01

    Specific identification of four clam species, Ruditapes decussatus (grooved carpet shell), Venerupis pullastra (pullet carpet shell), Ruditapes philippinarum (Japanese carpet shell), and Venerupis rhomboides (yellow carpet shell), was achieved by polymerase chain reaction-restriction fragment length polymorphism analysis of a fragment of the mitochondrial 16S rRNA gene. Amplification of DNA isolated from the foot muscle produced fragments of 511 bp for V. pullastra, 523 bp for R. decussatus, 545 bp for R. philippinarum, and 502 bp for V. rhomboides. The restriction profiles obtained by agarose gel electrophoresis when amplicons were digested with endonucleases BsmAI and BsrI allowed unequivocal identification of the four clam species. This approach would be less costly, simpler, and quicker than conventional sequencing of polymerase chain reaction products followed by detailed comparison of individual sequences, especially when large numbers of samples need to be analyzed.

  2. Gene Polymorphism Studies in a Teaching Laboratory

    NASA Astrophysics Data System (ADS)

    Shultz, Jeffry

    2009-02-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this example, students used genes annotated for the steroid biosynthesis pathway in soybean. The authoritative Kyoto encyclopedia of genes and genomes (KEGG) interactive database and other online resources were used to design primers based first on soybean expressed sequence tags (ESTs), then on ESTs from an alternate organism if soybean sequence was unavailable. Students designed a total of 50 gene-based primer pairs (37 soybean, 13 alternative) and tested these for polymorphism state and similarity between two soybean and two pea lines. Student assessment was based on acquisition of laboratory skills and successful project completion. This simple procedure illustrates conservation of genes and is not limited to soybean or pea. Cost per student estimates are included, along with a detailed protocol and flow diagram of the procedure.

  3. Identification of two distinct subsets of long-term nonprogressors with divergent viral activity by stromal-derived factor 1 chemokine gene polymorphism analysis.

    PubMed

    Balotta, C; Bagnarelli, P; Corvasce, S; Mazzucchelli, R; Colombo, M C; Papagno, L; Santambrogio, S; Ridolfo, A L; Violin, M; Berlusconi, A; Velleca, R; Facchi, G; Moroni, M; Clementi, M; Galli, M

    1999-08-01

    Stromal-derived factor (SDF)-1, the natural ligand for CXCR4, is present in a common polymorphic variant defined by a G-->A transition in the 3' untranslated region of the gene. In persons infected with human immunodeficiency virus type 1 (HIV-1), the homozygous genotype (SDF1-3'A/3'A) has been postulated to interfere with the appearance of T-tropic syncytium-inducing strains. The polymorphism of SDF1 was correlated with HIV-1 phenotype, plasma viremia, and unspliced and multiply spliced specific transcripts in 158 virologically characterized HIV-1-infected patients (39 recent seroconverters, 75 typical progressors, and 44 AIDS patients) and in 42 HIV-1-infected long-term nonprogressors (LTNPs). Analysis of SDF1 allele distribution revealed that SDF1-3'A/3'A status is associated with low CD4 cell count (P=.0449) but not with a specific HIV-1 phenotype. In LTNPs, SDF1-+/+ condition defined a subset of persons with lower HIV-1 replication than in heterozygous subjects. The low viral activity in SDF1-+/+ LTNPs suggests that other factors play a major role in vivo in determining the course of HIV-1 infection.

  4. Recent Male-Mediated Gene Flow over a Linguistic Barrier in Iberia, Suggested by Analysis of a Y-Chromosomal DNA Polymorphism

    PubMed Central

    Hurles, Matthew E.; Veitia, Reiner; Arroyo, Eduardo; Armenteros, Manuel; Bertranpetit, Jaume; Pérez-Lezaun, Anna; Bosch, Elena; Shlumukova, Maria; Cambon-Thomsen, Anne; McElreavey, Ken; López de Munain, Adolfo; Röhl, Arne; Wilson, Ian J.; Singh, Lalji; Pandya, Arpita; Santos, Fabrício R.; Tyler-Smith, Chris; Jobling, Mark A.

    1999-01-01

    Summary We have examined the worldwide distribution of a Y-chromosomal base-substitution polymorphism, the T/C transition at SRY-2627, where the T allele defines haplogroup 22; sequencing of primate homologues shows that the ancestral state cannot be determined unambiguously but is probably the C allele. Of 1,191 human Y chromosomes analyzed, 33 belong to haplogroup 22. Twenty-nine come from Iberia, and the highest frequencies are in Basques (11%; n=117) and Catalans (22%; n=32). Microsatellite and minisatellite (MSY1) diversity analysis shows that non-Iberian haplogroup-22 chromosomes are not significantly different from Iberian ones. The simplest interpretation of these data is that haplogroup 22 arose in Iberia and that non-Iberian cases reflect Iberian emigrants. Several different methods were used to date the origin of the polymorphism: microsatellite data gave ages of 1,650, 2,700, 3,100, or 3,450 years, and MSY1 gave ages of 1,000, 2,300, or 2,650 years, although 95% confidence intervals on all of these figures are wide. The age of the split between Basque and Catalan haplogroup-22 chromosomes was calculated as only 20% of the age of the lineage as a whole. This study thus provides evidence for direct or indirect gene flow over the substantial linguistic barrier between the Indo-European and non–Indo-European–speaking populations of the Catalans and the Basques, during the past few thousand years. PMID:10521311

  5. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    PubMed

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested