Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitus.

PubMed

Coskunoglu, Aysun; Orenay-Boyacioglu, Seda; Deveci, Artuner; Bayam, Mustafa; Onur, Ece; Onan, Arzu; Cam, Fethi S

2017-01-01

Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results.

Evidence of associations between brain-derived neurotrophic factor (BDNF) serum levels and gene polymorphisms with tinnitus

PubMed Central

Coskunoglu, Aysun; Orenay-Boyacioglu, Seda; Deveci, Artuner; Bayam, Mustafa; Onur, Ece; Onan, Arzu; Cam, Fethi S.

2017-01-01

Background: Brain-derived neurotrophic factor (BDNF) gene polymorphisms are associated with abnormalities in regulation of BDNF secretion. Studies also linked BDNF polymorphisms with changes in brainstem auditory-evoked response test results. Furthermore, BDNF levels are reduced in tinnitus, psychiatric disorders, depression, dysthymic disorder that may be associated with stress, conversion disorder, and suicide attempts due to crises of life. For this purpose, we investigated whether there is any role of BDNF changes in the pathophysiology of tinnitus. Materials and Methods: In this study, we examined the possible effects of BDNF variants in individuals diagnosed with tinnitus for more than 3 months. Fifty-two tinnitus subjects between the ages of 18 and 55, and 42 years healthy control subjects in the same age group, who were free of any otorhinolaryngology and systemic disease, were selected for examination. The intensity of tinnitus and depression was measured using the tinnitus handicap inventory, and the differential diagnosis of psychiatric diagnoses made using the Structured Clinical Interview for Fourth Edition of Mental Disorders. BDNF gene polymorphism was analyzed in the genomic deoxyribonucleic acid (DNA) samples extracted from the venous blood, and the serum levels of BDNF were measured. One-way analysis of variance and Chi-squared tests were applied. Results: Serum BDNF level was found lower in the tinnitus patients than controls, and it appeared that there is no correlation between BDNF gene polymorphism and tinnitus. Conclusions: This study suggests neurotrophic factors such as BDNF may have a role in tinnitus etiology. Future studies with larger sample size may be required to further confirm our results. PMID:28615544

CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

PubMed Central

Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

2015-01-01

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

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.

Associations Between Polymorphisms in the Glucocorticoid-Receptor Gene and Cardiovascular Risk Factors in a Chinese Population

PubMed Central

Yan, Yu-Xiang; Dong, Jing; Wu, Li-Juan; Shao, Shuang; Zhang, Jie; Zhang, Ling; Wang, Wei; He, Yan; Liu, You-Qin

2013-01-01

Background Glucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population. Methods We recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested. Results Among the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004). Conclusions Polymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease. PMID:23892712

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

PubMed Central

Chen, Jan-Yow; Liu, Jiung-Hsiun; Wu, Hong-Dar Isaac; Lin, Kuo-Hung; Chang, Kuan-Cheng; Liou, Ying-Ming

2016-01-01

Background Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome. Methods Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1. Results Two transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls. Conclusion Transforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome. PMID:27380173

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Amiri Jahromi, Rakhshan; Nasiri, Mahboobeh; Jahromi, Athar Rasekh

2017-01-01

This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran. 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease. These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.

Tumour necrosis factor (TNF)-α-308 gene polymorphism in Indian patients with Takayasu's arteritis - a pilot study.

PubMed

Sandhya, P; Danda, Sumita; Danda, Debashish; Lonarkar, Shraddha; Luke, Shana S; Sinha, Shanta; Joseph, George

2013-04-01

Tumour necrosis factor-alpha (TNF-α)- 308 promoter gene polymorphism has been shown to be associated with several autoimmune disorders and infections such as tuberculosis. There is no study on TNF-α gene polymorphism in Takayasu's arteritis (TA) till date. We aimed to study this polymorphism in TA, a granulomatous vasculitis, probably triggered by Mycobacterium tuberculosis. TNF-α - 308 gene polymorphism was studied in 34 patients with TA and 39 healthy controls recruited from Christian Medical College, India. PCR was done followed by enzyme digestion. G and A polymorphisms were analysed. Occurrence of alleles in the disease group was compared with controls as well as with historical controls. GG allele was most frequent in TA and in controls. GA allele was detected in four controls but only in one patient who was the oldest in the study group. AA polymorphism was detected in one control but not in TA. When compared with controls from other populations, it was found that our allelic frequency was similar to that in Japan as well as from USA with mixed population. However, predominantly Caucasian population studied from Netherlands, Germany and England, where TA is rare, had a higher frequency of A allele as compared to our controls. Our preliminary results indicated that G allele at TNF-α - 308 was more common in TA patients and controls similar to that in other Indian as well as Japanese population. Compared to the western population, A allele was relatively less common in our study subjects.

CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

PubMed

Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

2012-11-01

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. © 2012 John Wiley & Sons A/S.

Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics.

PubMed

Lien, Ming-Yu; Lin, Chiao-Wen; Tsai, Hsiao-Chi; Chen, Yng-Tay; Tsai, Ming-Hsui; Hua, Chun-Hung; Yang, Shun-Fa; Tang, Chih-Hsin

2017-05-09

In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.

Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics

PubMed Central

Lien, Ming-Yu; Lin, Chiao-Wen; Tsai, Hsiao-Chi; Chen, Yng-Tay; Tsai, Ming-Hsui; Hua, Chun-Hung; Yang, Shun-Fa; Tang, Chih-Hsin

2017-01-01

In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476–20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients. PMID:28404909

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

PubMed

Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

2015-05-15

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Association of cytokine gene polymorphisms and risk factors with otitis media proneness in children.

PubMed

Miljanović, Olivera; Cikota-Aleksić, Bojana; Likić, Dragan; Vojvodić, Danilo; Jovićević, Ognjen; Magić, Zvonko

2016-06-01

In order to assess the association between gene polymorphisms and otitis media (OM) proneness, tumor necrosis factor alpha (TNFA) -308, interleukin (IL) 10-1082 and -3575, IL6 -597, IL2 -330, and CD14 -159 genotyping was performed in 58 OM-prone children and 85 controls who were exposed to similar number and frequency of environmental and host risk factors. The frequencies of genotypes (wild type vs. genotypes containing at least one polymorphic allele) were not significantly different between groups, except for IL10 -1082. Polymorphic genotypes IL10 -1082 GA and GG were more frequent in OM-prone children than in control group (RR 1.145, 95 % CI 1.011-1.298; p = 0.047). However, logistic regression did not confirm IL10 -1082 polymorphic genotypes as an independent risk factor for OM proneness. The present study indicates that high-producing IL10 -1082 GA/GG genotypes may increase the risk for OM proneness in its carriers when exposed to other environmental/host risk factors (day care attendance, passive smoking, male sex, respiratory infections, and atopic manifestations). This study revealed no significant independent genetic association, but the lack of breastfeeding in infancy was found to be the only independent risk factor for development of OM-prone phenotype, implying that breastfeeding had a protective role in development of susceptibility to OM. • The pathogenesis of OM is of multifactorial nature, dependent on infection, environmental factors, and immune response of the child. • Cytokines and CD14 play an important role in the presentation and clinical course of otitis media, but a clear link with otitis media proneness was not established. What is new: • This is the first clinical and genetic study on Montenegrin children with the otitis media-prone phenotype. • The study revealed that high-producing IL10 -1082 genotypes may influence otitis media proneness in children exposed to other environmental/host risk factors.

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer.

PubMed

Qu, Yan-Li; Yu, Hong; Chen, Yan-Zhi; Zhao, Yu-Xia; Chen, Guang-Jun; Bai, Lu; Liu, Dan; Su, Hong-Xin; Wang, He-Tong

2014-09-01

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFβ1 -869 T/C, IL-6 -634C/G, TGFβ1 -509C/T, IL1 -511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a -889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a -889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G + G/G of IL6 -634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a -889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 -634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.

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.

MTHFR Gene Polymorphism-Mutations and Air Pollution as Risk Factors for Breast Cancer

PubMed Central

Gonzales, Mildred C.; Yu, Pojui; Shiao, S. Pamela K.

2017-01-01

Background The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. Objectives The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. Methods For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. Results We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. Discussion We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations. PMID:28114181

The correlation of leptin/leptin receptor gene polymorphism and insulin-like growth factor-1 and their impact on childhood growth hormone deficiency.

PubMed

He, J-S; Lian, C-W; Zhou, H-W; Lin, X-F; Yang, H-C; Ye, X-L; Zhu, S-B

2016-09-01

Growth hormone deficiency (GHD) is the most common cause for childhood dwarfism. Currently, the significance of insulin-like growth factor-1 (IGF-1) in diagnosis of GHD is still debatable. Due to the possible correlation between leptin (LEP) and GHD pathogenesis, this study investigated the gene polymorphism of LEP and its receptor (LEPR) genes, along with serum IGF-1 and LEP levels in GHD patients. This study attempted to illustrate the correlation between gene polymorphism and GHD pathogenesis. A case-control study was performed using 180 GHD children in addition to 160 healthy controls. PCR-DNA sequencing method was employed for genotyping various polymorphism loci of LEP and LEPR genes in both GHD and healthy individuals. Serum IGF-1 and LEP levels were also determined. Results revealed a statistically significant difference between the levels of IGF-1 and LEP in the serum samples collected from patients in the GHD and the control groups. Both IGF-1 and LEP levels were found to be correlated with polymorphism at rs7799039 loci of LEP gene, in which GG and GA genotypes carriers had higher serum IGF-1 levels when compared to AA genotype carriers. GHD pathogenesis is well correlated with the LEP and IGF-1 levels in the both of which were mediated by the gene polymorphism at rs7799039 loci of LEP gene.

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

PubMed

Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

2011-04-09

Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout.

PubMed

Chang, S-J; Tsai, P-C; Chen, C-J; Lai, H-M; Ko, Y-C

2007-11-01

To investigate the associations between polymorphisms in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene and gout. The polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106 gout patients and 159 healthy controls among male Taiwanese using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The biochemical markers, including Glutamic-oxaloacetic transaminase (GOT), Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol (TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as alcohol consumption were measured. The gout patients had 9.43% (10/106) with genotype AA at polymorphism -863C/A showing a significantly higher fraction than controls (0.63%; 1/159, P < 0.001). The crude results also showed that the gout patients had significantly higher portions of abnormal GOT, GPT, creatinine, TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P < 0.05), but the -308G/A, BMI and genotype CA at -863C/A did not show the same significant difference (P > 0.05). After adjustment by a stepwise logistic regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol consumption as well as genotype AA at polymorphism -863C/A were found to be significantly associated with gout. The genotype AA at polymorphism -863C/A in a recessive model showed a significant association with developing gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and alcohol consumption.

Association of -330 interleukin-2 gene polymorphism with oral cancer.

PubMed

Singh, Prithvi Kumar; Kumar, Vijay; Ahmad, Mohammad Kaleem; Gupta, Rajni; Mahdi, Abbas Ali; Jain, Amita; Bogra, Jaishri; Chandra, Girish

2017-12-01

Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer. The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated. IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (-330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers. Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.

Analysis of common transforming growth factor beta-1 gene polymorphisms in gastric and duodenal ulcer disease: pilot study.

PubMed

Polonikov, Alexey V; Ivanov, Vladimir P; Belugin, Dmitry A; Khoroshaya, Irina V; Kolchanova, Inessa O; Solodilova, Mariya A; Tutochkina, Margarita P; Stepchenko, Alexander A

2007-04-01

Transforming growth factor-beta1 (TGF-beta1) has been shown to be an important cytokine that plays a role in cell proliferation, differentiation, tissue injury repair and ulcer healing. The purpose of this pilot study was to investigate if common polymorphisms Leu10Pro, Arg25Pro and C-509T within the TGF-beta1 gene are associated with susceptibility to gastric and duodenal ulcer disease in Russians. Blood samples from 377 unrelated patients with gastric and duodenal ulcer disease and 226 sex- and age-matched healthy controls were used to determine TGF-beta1 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Leu10Pro substitution in the signal peptide of TGF-beta1 has been found to be associated with susceptibility to gastric ulcer (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.12-2.77). A genotype combination of 10Leu/Leu x 25Arg/Arg x -509C/C was also associated with susceptibility to gastric ulcer disease (OR 1.81, P = 0.01). In addition, the frequency of a combination of genotypes 10Pro/Pro x 25Arg/Pro x -509C/T was statistically lower in patients with duodenal ulcer than in controls (OR 0.42, P = 0.05). A significant difference (P = 0.04) in the distribution of rare haplotypes of the TGF-beta1 gene between patients with duodenal ulcer and healthy controls has been found. Polymorphism Leu10Pro was in positive linkage disequilibrium with C-509T polymorphism (coefficient D = 0.191; P < 0.0001). These findings indicate that the Leu10Pro and C-509T polymorphisms may be involved in the modulation of expression of the TGF-beta1 gene, and therefore a predisposition to peptic ulcer disease could be linked to particular alleles of this gene. In particular, a possible role of TGF-beta1 in the pathogenesis of gastric ulcer disease is discussed.

Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

PubMed

Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A

2006-09-01

Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fong, I.; Lai, P.S.; Ouah, T.C.

1994-09-01

The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1more » = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.« less

Heat shock protein 70-2 and tumor necrosis factor-α gene polymorphisms in Chinese children with Henoch-Schönlein purpura.

PubMed

Ding, Gui-Xia; Wang, Chen-Hu; Che, Ruo-Chen; Guan, Wan-Zhen; Yuan, Yang-Gang; Su, Min; Zhang, Ai-Hua; Huang, Song-Ming

2016-02-01

Henoch-Schönlein purpura (HSP) or IgA-associated vasculitis is related to immune disturbances. Polymorphisms of the heat shock protein 70-2 gene (HSP70-2) and the tumor necrosis factor-a gene (TNF-α) are known to be associated with immune diseases. The purpose of this study was to investigate the likely association of HSP70-2 (+1267A/G) and TNF-α (+308A/G) gene polymorphisms with HSP in children. The polymerase chain reaction restriction fragment length polymorphism method was used to detect the HSP70-2 and TNF-α polymorphisms in 205 cases of children with HSP and 53 controls; and the association of these polymorphisms with HSP and HSP nephritis (HSPN) was analyzed. The G/G genotypic frequencies at the +1267A/G position of HSP70-2 in the HSP group (22.9%) were significantly higher than those in the healthy control group (9.4%) (χ(2)=4.764, P<0.05). The frequencies of the A/A, A/G and G/G genotypes of HSP70-2 in patients in the nephritis-free group and the HSPN group showed no statistically significant difference. The A/A genotype frequency at the +308G/A position of TNF-α in the HSP group was 8.3%, which was higher than that in the control group (χ(2)=6.447, P<0.05). The A allele frequency of TNF-α in the HSP group was higher than that in the control group, with a statistically significant difference (χ(2)=7.241, P<0.05). The HSP70-2 (+1267A/G) and TNF-α (+308G/A) gene polymorphisms were associated with HSP in children. The G/G homozygosity of HSP70-2 and the A/A homozygosity of TNF-α may be genetic predisposing factors for HSP.

Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular Degeneration in an Iranian Population.

PubMed

Babanejad, Mojgan; Moein, Hamidreza; Akbari, Mohammad R; Badiei, Azadeh; Yaseri, Mehdi; Soheilian, Masoud; Najmabadi, Hossein

2016-06-01

Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population. We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy-Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPassoc. According to our results, the frequencies of risk allele for all SNPs (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170, respectively) were significantly higher in AMD patients (p value < 0.001). AMD individuals who had at least one copy of the C allele of rs1061170 had an increased risk of disease compared with cases with the T allele. Other studied polymorphisms showed the same association. Our results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population. This association with CFH may lead to early detection and new strategies for prevention and treatment of AMD.

[Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].

PubMed

Liu, Qi-Ji; Gong, Yao-Qin; Guo, Chen-Hong; Chen, Bing-Xi; Li, Jiang-Xia; Guo, Yi-Shou

2002-01-01

To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene.

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

PubMed

Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

2007-10-19

Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

Polymorphisms in TAS2R38 and the taste bud trophic factor, gustin gene co-operate in modulating PROP taste phenotype.

PubMed

Calò, Carla; Padiglia, Alessandra; Zonza, Andrea; Corrias, Laura; Contu, Paolo; Tepper, Beverly J; Barbarossa, Iole Tomassini

2011-10-24

The PROP taste phenotype varies greatly among individuals, influencing eating behavior and therefore may play a role in body composition. This variation is associated with polymorphisms in the bitter receptor gene TAS2R38 and the taste-bud trophic factor gustin gene. The aim of this study was to examine the relationship between TAS2R38 haplotypes and the gustin gene polymorphism rs2274333 in modulating PROP taste phenotype. PROP phenotype was determined in seventy-six volunteers (29 males, 47 females, age 25±3 y) by scaling methods and threshold measurements. TAS2R38 and gustin gene genotyping was performed using PCR techniques. The lowest responsiveness in PROP nontasters is strongly associated with the AVI nontasting TAS2R38 variant and the highest responsiveness in supertasters is strongly associated to allele A and genotype AA of the gustin gene. These data support the hypothesis that the greater sensitivity of supertasters could be mediated by a greater taste-bud density. Polymorphisms in TAS2R38 and gustin gene, together, accounted for up to 60% of the phenotypic variance in PROP bitterness and to 40% in threshold values. These data, suggest that other unidentified factors may be more relevant for detecting low concentrations of PROP. Moreover, the presence of the PAV variant receptor may be important for detecting high concentrations of PROP, whereas the presence of allele A in gustin polymorphism may be relevant for perceiving low concentrations. These data show how the combination of the TAS2R38 and gustin gene genotypes modulate PROP phenotype, providing an additional tool for the evaluation of human eating behavior and nutritional status. Copyright © 2011 Elsevier Inc. All rights reserved.

Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

PubMed

Chang, Y T; Liu, H N; Yu, C W; Lin, M W; Huang, C H; Chen, C C; Liu, M T; Lee, D D; Wang, W J; Tsai, S F

2006-01-01

Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

PubMed

Yang, Po-Yu; Miao, Nae-Fang; Lin, Chiao-Wen; Chou, Ying-Erh; Yang, Shun-Fa; Huang, Hui-Chuan; Chang, Hsiu-Ju; Tsai, Hsiu-Ting

2016-01-01

The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

PubMed Central

Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

2004-01-01

The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder.

PubMed

Betancur, C; Corbex, M; Spielewoy, C; Philippe, A; Laplanche, J L; Launay, J M; Gillberg, C; Mouren-Siméoni, M C; Hamon, M; Giros, B; Nosten-Bertrand, M; Leboyer, M

2002-01-01

Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 2 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants. Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele and the other of the long allele. Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus. These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects. Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism.

Apolipoprotein E gene polymorphism and gender.

PubMed

Kolovou, Genovefa; Damaskos, Dimitris; Anagnostopoulou, Katherine; Cokkinos, Dennis V

2009-01-01

Many studies have shown that the prevalence and onset of coronary heart disease (CHD) is sex-dependent. CHD prevalence is lower in women than in men at all ages. Furthermore, women's age of CHD onset seems to be 10 yr later. This is widely attributed to the fact that men have less favorable CHD risk factors (eg, plasma lipid profile) compared to women. Mean levels of protective high density lipoprotein cholesterol are lower, while triglyceride levels are higher in men than in women. It is possible that many of the genes involved in lipid metabolism, such as Apolipoprotein (Apo) E, as well as their polymorphisms, may be expressed in a sexually dimorphic manner. The human Apo E gene is polymorphic, encoding one of 3 common epsilon (epsilon) alleles (epsilon 2, epsilon 3, epsilon 4), with the epsilon 3 allele occurring most frequently (78%) in the Caucasian population. Association studies have shown a protective effect on CHD in epsilon 2 carriers and a harmful effect in epsilon 4 carriers. However, there are conflicting results regarding such allelic effects in respect to gender. This review is focused on the gender-related influence of Apo E polymorphism in respect to plasma lipid levels and the risk of CHD. Additionally, an effort is made to determine if this relation exists and if it can be satisfactorily explained. The studies cited here demonstrate a complex, multifactorial association between these factors, in need of further corroboration in greater population samples.

Interactions of Environmental Factors and APOA1-APOC3-APOA4-APOA5 Gene Cluster Gene Polymorphisms with Metabolic Syndrome.

PubMed

Wu, Yanhua; Yu, Yaqin; Zhao, Tiancheng; Wang, Shibin; Fu, Yingli; Qi, Yue; Yang, Guang; Yao, Wenwang; Su, Yingying; Ma, Yue; Shi, Jieping; Jiang, Jing; Kou, Changgui

2016-01-01

The present study investigated the prevalence and risk factors for Metabolic syndrome. We evaluated the association between single nucleotide polymorphisms (SNPs) in the apolipoprotein APOA1/C3/A4/A5 gene cluster and the MetS risk and analyzed the interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS. A study on the prevalence and risk factors for MetS was conducted using data from a large cross-sectional survey representative of the population of Jilin Province situated in northeastern China. A total of 16,831 participations were randomly chosen by multistage stratified cluster sampling of residents aged from 18 to 79 years in all nine administrative areas of the province. Environmental factors associated with MetS were examined using univariate and multivariate logistic regression analyses based on the weighted sample data. A sub-sample of 1813 survey subjects who met the criteria for MetS patients and 2037 controls from this case-control study were used to evaluate the association between SNPs and MetS risk. Genomic DNA was extracted from peripheral blood lymphocytes, and SNP genotyping was determined by MALDI-TOF-MS. The associations between SNPs and MetS were examined using a case-control study design. The interactions of environmental factors and APOA1/C3/A4/A5 gene cluster polymorphisms with MetS were assessed using multivariate logistic regression analysis. The overall adjusted prevalence of MetS was 32.86% in Jilin province. The prevalence of MetS in men was 36.64%, which was significantly higher than the prevalence in women (29.66%). MetS was more common in urban areas (33.86%) than in rural areas (31.80%). The prevalence of MetS significantly increased with age (OR = 8.621, 95%CI = 6.594-11.272). Mental labor (OR = 1.098, 95%CI = 1.008-1.195), current smoking (OR = 1.259, 95%CI = 1.108-1.429), excess salt intake (OR = 1.252, 95%CI = 1.149-1.363), and a fruit and dairy intake less than 2 servings a week were

Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiang, R.; Lidral, A.C.; Ardinger, H.H.

1993-10-01

Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. The authors carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3[prime] untranslated region ofmore » the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using X[sup 2] analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3[prime] untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P. 46 refs., 3 figs., 3 tabs.« less

R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

PubMed Central

2011-01-01

Background Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels. PMID:21477332

Association of interleukin 8 -251 A/T gene polymorphism with periodontitis in Indonesia

NASA Astrophysics Data System (ADS)

Jessica, C.; Alwadris, T. T.; Prasetyo, S. R.; Puspitawati, R.; Auerkari, E. I.

2018-05-01

Periodontitis is a chronic multifactorial disease resulting from an interaction between periodontal pathogen bacteria, host, and environmental factors. Genetics has been identified to contribute to the pathogenesis and susceptibility of periodontitis, and interleukin 8 (IL-8) gene is expressing one of the chemokines involved in the inflammation process. This study aimed to evaluate the association of IL-8 -251 A/T gene polymorphism with periodontitis in Indonesian subjects. The study was conducted by genotyping 72 samples of patients with various severity of periodontitis and 41 samples of healthy controls group using PCR-RFLP method. Genotypes of the IL-8 gene polymorphism in periodontitis patients were not significantly different with those in healthy controls. Those with TT genotype were 3.40 times less likely to develop periodontitis compared to AA genotype (95% CI). There was a significant difference in allele frequencies (p < 0.05, OR = 1.828, 95% CI), suggesting that allele T is a risk factor to periodontitis. Statistical analyses with Chi-square testing showed no significant association of IL-8 -251 A/T gene polymorphism and the severity of periodontitis in Indonesia. However, IL-8 -251 A/T gene polymorphism might contribute to the susceptibility of periodontitis.

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

PubMed Central

Wiersma, Anje C; Leegwater, Peter AJ; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

2007-01-01

Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies. PMID:17949487

The evaluation of angiotensin-converting enzyme (ACE) gene I/D and IL-4 gene intron 3 VNTR polymorphisms in coronary artery disease.

PubMed

Basol, Nursah; Celik, Atac; Karakus, Nevin; Ozturk, Sibel Demir; Ozsoy, Sibel Demir; Yigit, Serbulent

2014-01-01

Genetic polymorphism is a strong risk factor for coronary artery disease (CAD). In the present study, our aim was to evaluate angiotensin-converting enzyme (ACE) gene I/D polymorphism and interleukin-4 (IL-4) gene Intron 3 variable number of tandem repeat (VNTR) polymorphism in CAD. One hundred and twenty-four CAD patients and one hundred and twenty-three controls were enrolled. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses. The risk associated with inheriting the combined genotypes for the two polymorphisms were evaluated and it was found that the individuals who were P2P2-homozygous at IL-4 gene intron 3 VNTR and DD-homozygous at ACE gene I/D have a higher risk of developing CAD. Although, there is no correlation between IL4 VNTR polymorphism and ACE gene polymorphism and CAD, there is a strong association between CAD and co-existence of IL-4 VNTR and ACE gene polymorphisms in the Turkish population. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Are "functionally related polymorphisms" of renin-angiotensin-aldosterone system gene polymorphisms associated with hypertension?

PubMed

Hahntow, Ines N; Mairuhu, Gideon; van Valkengoed, Irene Gm; Koopmans, Richard P; Michel, Martin C

2010-06-02

Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may have stronger phenotype associations than those within a single gene. We have tested this hypothesis using genes encoding components of the renin-angiotensin-aldosterone system and the high blood pressure phenotype. Our analysis is based on 1379 participants of the cross-sectional SUNSET study randomly selected from the population register of Amsterdam. Each subject was genotyped for the angiotensinogen M235T, the angiotensin-converting enzyme insertion/deletion and the angiotensin II type 1 receptor A1166C polymorphism. The phenotype high blood pressure was defined either as a categorical variable comparing hypertension versus normotension as in most previous studies or as a continuous variable using systolic, diastolic and mean blood pressure in a multiple regression analysis with gender, ethnicity, age, body-mass-index and antihypertensive medication as covariates. Genotype-phenotype relationships were explored for each polymorphism in isolation and for double and triple polymorphism combinations. At the single polymorphism level, only the A allele of the angiotensin II type 1 receptor was associated with a high blood pressure phenotype. Using combinations of polymorphisms of two or all three genes did not yield stronger/more consistent associations. We conclude that combinations of physiologically related polymorphisms of multiple genes, at least with regard to the renin-angiotensin-aldosterone system and the hypertensive phenotype, do not necessarily offer additional benefit in analyzing genotype/phenotype associations.

Vascular endothelial growth factor-A gene polymorphism is associated with congenital renal lesions in children with urinary tract infections.

PubMed

Bimpaki, Eirini; Bitsori, Maria; Choulaki, Christiana; Galanakis, Emmanouil

2017-08-01

This study investigated the relationship between vascular endothelial growth factor-A (VEGF-A)-460C/T functional gene polymorphism and renal parenchymal lesions, vesicoureteral reflux and other urinary tract abnormalities in children with a urinary tract infection (UTI). VEGF-A-460C/T gene polymorphism was investigated with restriction length polymorphism analysis in 76 children with their first UTI and in 63 controls without infections. Genotype and allele frequencies were compared between children with UTIs and controls and between different groups with UTIs. The VEGF-A-460C/T genotype frequencies differed significantly between those with and without renal parenchymal lesions in the UTI cohort. Allele C homozygosity was significantly more common in those with renal parenchymal lesions (36.6% versus 8.7%, p = 0.007). A separate analysis showed that allele C was associated with lesions compatible with hypodysplasia, rather than with focal ones associated with infections, with an odds ratio of 11.55 and 95% confidence interval of 3.03-43.9 (p = 0.0001). No significant differences in genotypes or allele frequencies were found between children with and without reflux or other urinary tract anomalies. In children with UTIs, C allele polymorphism of the VEGF-A gene was associated with hypodysplastic renal parenchymal lesions, which were possibly congenital and existed before the infection. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The rs4285184 polymorphism of the MGAT1 gene as a risk factor for obesity in the Mexican population.

PubMed

Tapia-Rivera, José C; Baltazar-Rodríguez, Luz M; Cárdenas-Rojas, Martha I; Álvarez, Alan; Bustos-Saldaña, Rafael; Delgado-Enciso, Iván; Valdez-Velázquez, Laura L; Guzmán-Esquivel, José; Ramírez-Flores, Mario

2017-02-23

Obesity is a factor that contributes to the morbidity of certain diseases and to worldwide mortality. MGAT1 is a glycosyltransferase involved in the synthesis of protein-bound and lipid-bound oligosaccharides and its polymorphisms are possibly involved in the etiology of obesity. We investigated the association of the rs4285184 polymorphism of the MGAT1 gene with obesity in adults in the State of Colima, Mexico. A case-control study was conducted that included 244 subjects. All of them were grouped according to their percentage of body fat, determined through bioelectrical impedance, and they were genotyped for the rs4285184 polymorphism of the MGAT1 gene through PCR-RFLP. The results were analyzed for their association with the percentage of body fat. The G allele had a frequency of 49.19 and 38.75% for the cases and controls, respectively (P=.020) (OR 1.53; 95% CI 1.068-2.193). The frequency of the A/G+G/G genotype was 75% in the obese patients, which was significantly higher compared with the 57.5% of the control group (P=.004) (OR 2.217; 95% CI 1.287-3.821). The presence of the rs4285184 polymorphism of the MGAT1 gene increased the risk for developing body fat associated with obesity in the Mexican population. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder

PubMed Central

Betancur, Catalina; Corbex, Marylis; Spielewoy, Cécile; Philippe, Anne; Laplanche, Jean-Louis; Launay, Jean-Marie; Gillberg, Christopher; Mouren-Simeoni, Marie-Christine; Hamon, Michel; Giros, Bruno; Nosten-Bertrand, Marika; Leboyer, Marion

2002-01-01

Previous studies have provided conflicting evidence regarding the association of the serotonin transporter (5-HTT) gene with autism. Two polymorphisms have been identified in the human 5-HTT gene, a VNTR in intron 21 and a functional deletion/insertion in the promoter region (5-HTTLPR) with short and long variants.2 Positive associations of the 5-HTTLPR polymorphism with autism have been reported by two family-based studies, but one found preferential transmission of the short allele3 and the other of the long allele.4 Two subsequent studies failed to find evidence of transmission disequilibrium at the 5-HTTLPR locus.5,6 These conflicting results could be due to heterogeneity of clinical samples with regard to serotonin (5-HT) blood levels, which have been found to be elevated in some autistic subjects.7–9 Thus, we examined the association of the 5-HTTLPR and VNTR polymorphisms of the 5-HTT gene with autism, and we investigated the relationship between 5-HTT variants and whole-blood 5-HT. The transmission/disequilibrium test (TDT) revealed no linkage disequilibrium at either loci in a sample of 96 families comprising 43 trios and 53 sib pairs. Furthermore, no significant relationship between 5-HT blood levels and 5-HTT gene polymorphisms was found. Our results suggest that the 5-HTT gene is unlikely to play a major role as a susceptibility factor in autism. PMID:11803447

[Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetics].

PubMed

Olmos, P; Acosta, A M; Schiaffino, R; Díaz, R; Alvarado, D; O'Brien, A; Muñoz, X; Arriagada, P; Claro, J C; Vega, R; Vollrath, V; Velasco, S; Emmerich, M; Maiz, A

1999-04-01

Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.

Associations of SAA1 gene polymorphism with lipid lelvels and osteoporosis in Chinese women.

PubMed

Feng, Zheng-Ping; Li, Xiao-Yu; Jiang, Rong; Deng, Hua-Cong; Yang, Mei; Zhou, Qin; Que, Wen-Jun; Du, Jia

2013-03-22

The development of osteoporosis is associated with several risk factors, such as genetic polymorphisms and enviromental factors. This study assessed the correlation between SAA1 gene rs12218 polymorphism and HDL-C lelvels and osteoporosis in a population of Chinese women. A total of 387 postmenopausal female patients who were diagnosed with osteoporosis (case group) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 307 females with no osteoporosis (control group) were included in this study. Correlations between SAA1 gene rs12218 polymorphism and osteoporosis and HDL-C level were investigated through the identification of SAA1 gene rs12218 polymorphism genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The TT genotype of rs12218 was more frequently in osteoporosis patients than in control subjects (P <0.001). And the rs12218 was found to be associated with plasma TG, HDL-C, LDL-C, and BMD levels in osteoporosis patients (P<0.05). The present results indicate that both osteoporosis and lipids levels are associated with the TT genotype of rs12218 in the human SAA1 gene.

Associations of SAA1 gene polymorphism with Lipid lelvels and osteoporosis in Chinese women

PubMed Central

2013-01-01

Background The development of osteoporosis is associated with several risk factors, such as genetic polymorphisms and enviromental factors. This study assessed the correlation between SAA1 gene rs12218 polymorphism and HDL-C lelvels and osteoporosis in a population of Chinese women. Methods A total of 387 postmenopausal female patients who were diagnosed with osteoporosis (case group) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 307 females with no osteoporosis (control group) were included in this study. Correlations between SAA1 gene rs12218 polymorphism and osteoporosis and HDL-C level were investigated through the identification of SAA1 gene rs12218 polymorphism genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The TT genotype of rs12218 was more frequently in osteoporosis patients than in control subjects (P <0.001). And the rs12218 was found to be associated with plasma TG, HDL-C, LDL-C, and BMD levels in osteoporosis patients (P<0.05). Conclusions The present results indicate that both osteoporosis and lipids levels are associated with the TT genotype of rs12218 in the human SAA1 gene. PMID:23522429

[Prevalence of gene polymorphisms associated with immune-dependent diseases in the populations of North Eurasia].

PubMed

Cherednichenko, A A; Trifonova, E A; Vagaitseva, K V; Bocharova, A V; Varzari, A M; Radzhabov, M O; Stepanov, V A

2015-01-01

The data on distribution of genetic diversity in gene polymorphisms associated with autoimmune and allergic diseases and with regulation of immunoglobulin E and cytokines levels in 26 populations of the Northern Eurasia is presented. Substantial correlation between the values of average expected heterozygosity by 44 gene polymorphisms with climatic and geographical factors has not been revealed. Clustering of population groups in correspondence with their geographic locations is observed. The degree of gene differentiation among populations and the selective neutrality of gene polymorphisms have been assessed. The results of our work evidence the substantial genetic diversity and differentiation of human populations by studied genes.

MAOA and TNF-β gene polymorphisms are associated with photophobia but not osmophobia in patients with migraine.

PubMed

Ishii, Masakazu; Usami, Shino; Hara, Hajime; Imagawa, Atsuko; Masuda, Yutaka; Shimizu, Shuniichi

2014-06-01

Photophobia and osmophobia are typical symptoms associated with migraine, but the contributions of gene polymorphisms to these symptoms are not fully elucidated. We investigated whether the gene polymorphisms are involved in photophobia and osmophobia in patients with migraine. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms were determined by polymerase-chain-reaction (PCR) and PCR restriction-fragment-length polymorphism analysis. Photophobia and osmophobia were observed in 49 (54%) and 31 patients (34%), respectively. Distributions of monoamine oxidase A (MAOA) T941G and tumour necrosis factor-β (TNF-β) G252A polymorphisms were significantly different between patients with photophobia and controls. However, no gene polymorphism differences were observed between patients with osmophobia and controls. The MAOA T941G and TNF-β G252A gene polymorphisms appear to contribute to photophobia but not to osmophobia. We propose that different gene polymorphisms are responsible for photophobia and osmophobia symptoms during migraine.

Pre-B-cell colony-enhancing factor gene polymorphisms and risk of acute respiratory distress syndrome.

PubMed

Bajwa, Ednan K; Yu, Chu-Ling; Gong, Michelle N; Thompson, B Taylor; Christiani, David C

2007-05-01

Pre-B-cell colony-enhancing factor (PBEF) levels are elevated in bronchoalveolar lavage fluid and serum of patients with acute lung injury. There are several suspected functional polymorphisms of the corresponding PBEF gene. We hypothesized that variations in PBEF gene polymorphisms alter the risk of developing acute respiratory distress syndrome (ARDS). Nested case-control study. Tertiary academic medical center. We studied 375 patients with ARDS and 787 at-risk controls genotyped for the PBEF T-1001G and C-1543T polymorphisms. None. Patients with the -1001G (variant) allele had significantly greater odds of developing ARDS than wild-type homozygotes (odds ratio, 1.35; 95% confidence interval, 1.02-1.78). Patients with the -1543T (variant) allele did not have significantly different odds of developing ARDS than wild-type homozygotes (odds ratio, 0.86; 95% confidence interval, 0.65-1.13). When analysis was stratified by ARDS risk factor, -1543T was associated with decreased odds of developing ARDS in septic shock patients (odds ratio, 0.66; 95% confidence interval, 0.45-0.97). Also, -1001G was associated with increased hazard of intensive care unit mortality, whereas -1543T was associated with decreased hazard of 28-day and 60-day ARDS mortality, as well as shorter duration of mechanical ventilation. Similar results were found in analyses of the related GC (-1001G:-1543C) and TT (-1001T:-1543T) haplotypes. The PBEFT-1001G variant allele and related haplotype are associated with increased odds of developing ARDS and increased hazard of intensive care unit mortality among at-risk patients, whereas the C-1543T variant allele and related haplotype are associated with decreased odds of ARDS among patients with septic shock and better outcomes among patients with ARDS.

DNA Polymorphism of Insulin-like Growth Factor-binding Protein-3 Gene and Its Association with Cashmere Traits in Cashmere Goats

PubMed Central

Liu, Haiying; Liu, Chao; Yang, Guiqin; Li, Hui; Dai, Jin; Cong, Yuyan; Li, Xuejian

2012-01-01

Insulin-like growth factor binding protein-3 (IGFBP-3) gene is important for regulation of growth and development in mammals. The present investigation was carried out to study DNA polymorphism by PCR-RFLP of IGFBP-3 gene and its effect on fibre traits of Chinese Inner Mongolian cashmere goats. The fibre traits data investigated were cashmere fibre diameter, combed cashmere weight, cashmere fibre length and guard hair length. Four hundred and forty-four animals were used to detect polymorphisms in the hircine IGFBP-3 gene. A 316-bp fragment of the IGFBP-3 gene in exon 2 was amplified and digested with HaeIII restriction enzyme. Three patterns of restriction fragments were observed in the populations. The frequency of AA, AB and BB genotypes was 0.58, 0.33 and 0.09 respectively. The allelic frequency of the A and B allele was 0.75 and 0.25 respectively. Nucleotide sequencing revealed a C>G transition in the exon 2 region of the IGFBP-3 gene resulting in R158G change which caused the polymorphism. Least squares analysis revealed a significant effect of genotypes on cashmere weight (p<0.0001), cashmere fibre length (p<0.001) and hair length (p<0.05) of the animals. The effect of genotypes on cashmere fibre diameter was not statistically significant (p>0.05). The animals of AB and BB genotypes showed higher cashmere weight, cashmere fibre length and hair length than the animals possessing AA genotype. These results suggested that polymorphisms in the hircine IGFBP-3 gene might be a potential molecular marker for cashmere weight in cashmere goats. PMID:25049511

Relationship of MTHFR gene polymorphisms with renal and cardiac disease

PubMed Central

Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

2015-01-01

AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

PubMed

Butov, Dmytro O; Kuzhko, Mykhaylo M; Makeeva, Natalia I; Butova, Tetyana S; Stepanenko, Hanna L; Dudnyk, Andrii B

2016-01-01

Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines' production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene.

PubMed

Eskafi Sabet, E; Salehi, Z; Khodayari, S; Sabouhi Zarafshan, S; Zahiri, Z

2015-02-01

Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

PubMed

Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

2017-01-01

Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis.

PubMed

Mamyrova, Gulnara; O'Hanlon, Terrance P; Sillers, Laura; Malley, Karen; James-Newton, Laura; Parks, Christina G; Cooper, Glinda S; Pandey, Janardan P; Miller, Frederick W; Rider, Lisa G

2008-12-01

To study tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1) cytokine polymorphisms as possible risk and protective factors, define their relative importance, and examine these as severity factors in patients with juvenile dermatomyositis (DM). TNFalpha and IL-1 cytokine polymorphism and HLA typing were performed in 221 Caucasian patients with juvenile DM, and the results were compared with those in 203 ethnically matched healthy volunteers. The genotypes TNFalpha -308AG (odds ratio [OR] 3.6), TNFalpha -238GG (OR 3.5), and IL-1alpha +4845TT (OR 2.2) were risk factors, and TNFalpha -308GG (OR 0.26) as well as TNFalpha -238AG (OR 0.22) were protective, for the development of juvenile DM. Carriage of a single copy of the TNFalpha -308A (OR 3.8) or IL-1beta +3953T (OR 1.7) allele was a risk factor, and the TNFalpha -238A (OR 0.29) and IL-1alpha +4845G (OR 0.46) alleles were protective, for juvenile DM. Random Forests classification analysis showed HLA-DRB1*03 and TNFalpha -308A to have the highest relative importance as risk factors for juvenile DM compared with the other alleles (Gini scores 100% and 90.7%, respectively). TNFalpha -308AA (OR 7.3) was a risk factor, and carriage of the TNFalpha -308G (OR 0.14) and IL-1alpha -889T (OR 0.41) alleles was protective, for the development of calcinosis. TNFalpha -308AA (OR 7.0) was a possible risk factor, and carriage of the TNFalpha -308G allele (OR 0.14) was protective, for the development of ulcerations. None of the studied TNFalpha, IL-1alpha, and IL-1beta polymorphisms were associated with the disease course, disease severity at the time of diagnosis, or the patient's sex. TNFalpha and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity.

Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation.

PubMed

Zhang, Wu; Park, David J; Lu, Bo; Yang, Dong Yun; Gordon, Michael; Groshen, Susan; Yun, Jim; Press, Oliver A; Vallböhmer, Daniel; Rhodes, Katrin; Lenz, Heinz-Josef

2005-01-15

An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.

Factor IX gene haplotypes in Amerindians.

PubMed

Franco, R F; Araújo, A G; Zago, M A; Guerreiro, J F; Figueiredo, M S

1997-02-01

We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

TGF-β Polymorphisms Are a Risk Factor for Chagas Disease.

PubMed

Ferreira, Roberto Rodrigues; Madeira, Fabiana da Silva; Alves, Gabriel Farias; Chambela, Mayara da Costa; Curvo, Eduardo de Oliveira Vaz; Moreira, Aline Dos Santos; Almeida de Sá, Renata; Mendonça-Lima, Leila; Cabello, Pedro Hernan; Bailly, Sabine; Feige, Jean-Jacques; Araujo-Jorge, Tania Cremonini; Saraiva, Roberto Magalhães; Waghabi, Mariana Caldas

2018-01-01

Transforming growth factor β 1 (TGF- β 1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF- β 1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (-800 G>A, -509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position -509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, -509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population.

Renin Gene Polymorphisms in Bangladeshi Hypertensive Population

PubMed Central

Afruza, Rownock; Islam, Laila N; Banerjee, Sajal; Hassan, Md. Mahbub; Suzuki, Fumiaki; Nabi, AHM Nurun

2014-01-01

Objective: Linkages of renin gene polymorphisms with hypertension have been implicated in several populations with contrasting results. Present study aims to assess the pattern of renin gene polymorphisms in Bangladeshi hypertensive individuals. Methodology: Introns 1, 9 of renin gene and 4063 bases upstream of promoter sequence of renin gene were amplified from the genomic DNA of the total 124 (hypertensive and normotensive) subjects using respective primers. Polymerase chain reaction-based restriction fragment length polymorphisms were performed using BglI, MboI and TaqI restriction enzymes. Results: Homozygosity was common in renin gene regarding BglI (bb=48.4%, Bb=37.9%, BB=13.7%, χ2 =1.91, P>0.05), TaqI (TT=81.5%, Tt=14.5%, tt=4.0%, χ2 =7.50, P<0.01) and MboI (mm=63.7%, Mm=32.3%, MM=4.0%, χ2=0.00, P>0.05) polymorphisms among total study population. For BglI and TaqI genotype distribution, hypertensive subjects (BglI: χ2 =6.66, P<0.05; TaqI: χ2 = 10.28, P<0.005) significantly deviate from Hardy-Weinberg Equilibrium law compared to normotensive subjects (BglI: χ2=0.51, P>0.05; TaqI: χ2=0.20, P>0.05). On the other hand, with respect to MboI polymorphisms of renin gene, only normotensive subjects deviate from the law (patients: χ2=1.28, P>0.05; vs controls: χ2=6.81, P<0.01). In the context of allelic frequency, common T allele was clearly prevalent (T frequency=0.86, t frequency = 0.14) for TaqI, but rare alleles b and m were more frequent for both BglI (b frequency=0.69, B frequency=0.31) and MboI (m frequency=0.80 M frequency=0.20) polymorphisms, respectively. Conclusion: Thus, we report that Bangladeshi hypertensive subjects did not show any distinct pattern of renin gene polymorphisms compared to their healthy control subjects with regard to their genotypic and allelic frequencies. PMID:25057323

Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma.

PubMed

Sivaprasad, Siddapuram; Govardhan, Bale; Harithakrishna, Ramanujam; Venkat Rao, Guduru; Pradeep, Rebala; Kunal, Bharadhwaj; Ramakrishna, Nalla; Anuradha, Shekaran; Reddy, Duvvuru Nageshwar

2013-01-01

BACKGROUND &AIM: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level. Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay. The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P = 0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P > 0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD ± 230.79) when compared to controls (591.35 pg/mL, SD ± 92.48) (P < 0.0001), which showed a strong genotype-phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level. The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Gene polymorphisms of epidermal growth factor receptor and its downstream effector, interleukin-8, predict oxaliplatin efficacy in patients with advanced colorectal cancer.

PubMed

Zhang, Wu; Stoehlmacher, Jan; Park, David J; Yang, Dongyun; Borchard, Erin; Gil, Ji; Tsao-Wei, Denice D; Yun, Jim; Gordon, Michael; Press, Oliver A; Rhodes, Katrin; Groshen, Susan; Lenz, Heinz-Josef

2005-07-01

Researchers have recently reported an association between the epidermal growth factor receptor (EGFR) pathway and platinum-chemotherapy sensitivity in cancer patients. The (CA)(n) repeat polymorphism in intron 1 of the EGFR gene has been identified and found to alter EGFR expression in vitro as well as in vivo. A higher number of these CA repeats is associated with lower EGFR levels, whereas a low number of repeats is associated with higher EGFR levels. A second key polymorphism within the EGFR pathway (HER1 R497K) is a single nucleotide change (G-A) in codon 497 of the EGFR gene, which leads to an arginine-lysine substitution in the extracellular domain of subdomain IV. Furthermore, interleukin-8 (IL-8), recently identified as an EGFR downstream effector, plays a vital role in tumor angiogenesis and progression. Three other polymorphisms, each related to the IL-8 gene, have also been identified as playing a pivotal role in the EGFR pathway: T-251A in the promoter region of the IL-8 gene, G+2607C in exon 2 of the IL-8 receptor CXCR1 gene, and C+785T in exon 11 of the IL-8 receptor CXCR2 gene. In this study, we employed a 5'-end 33P-gATP-labeled polymerase chain reaction (PCR) protocol as well as the PCR-restriction fragment length polymorphism method in order to determine the genotypes for the previously mentioned polymorphisms in 105 patients with metastatic colorectal cancer. Tests were conducted to establish whether these polymorphisms could predict clinical outcome to 5-flourouracil/oxaliplatin chemotherapy. Among all patients assessed, those possessing < 20 EGFR CA repeats were more likely to show disease progression than were patients with >or= 20 CA repeats (P = 0.019; log-rank test). Also, patients with the CXCR1 GC genotype were found to have an increased relative risk of time to tumor progression that was 1.55 (95% CI, 0.8-3.0) times that of patients with the homozygous GG genotype (P = 0.17; log-rank test). Overall, our data suggest that gene

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

PubMed Central

van Manen, Daniëlle; Bunnik, Evelien M.; van Sighem, Ard I.; Sieberer, Margit; Boeser-Nunnink, Brigitte; de Wolf, Frank; Schuitemaker, Hanneke; Portegies, Peter; Kootstra, Neeltje A.; van 't Wout, Angélique B.

2012-01-01

Background Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. Methods We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. Results The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2×10−5). Prep1 has recently been identified as a transcription factor preferentially binding the −2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. Conclusion These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders. PMID:22347417

Clinical relevance of IL-6 gene polymorphism in severely injured patients

PubMed Central

Jeremić, Vasilije; Alempijević, Tamara; Mijatović, Srđan; Šijački, Ana; Dragašević, Sanja; Pavlović, Sonja; Miličić, Biljana; Krstić, Slobodan

2014-01-01

In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL-6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism. PMID:24856384

Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T) as a Risk Factor for Arterial Thrombosis in Georgian Patients.

PubMed

Garakanidze, Sopio; Costa, Elísio; Bronze-Rocha, Elsa; Santos-Silva, Alice; Nikolaishvili, Giorgi; Nakashidze, Irina; Kakauridze, Nona; Glonti, Salome; Khukhunaishvili, Rusudan; Koridze, Marina; Ahmad, Sarfraz

2018-01-01

Methylenetetrahydrofolate reductase ( MTHFR) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 ± 12.1 years) and 113 controls (67.3% males; mean age: 56.6 ± 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group ( P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients.

MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine.

PubMed

Ishii, Masakazu; Shimizu, Shunichi; Sakairi, Yuki; Nagamine, Ayumu; Naito, Yuika; Hosaka, Yukiko; Naito, Yuko; Kurihara, Tatsuya; Onaya, Tomomi; Oyamada, Hideto; Imagawa, Atsuko; Shida, Kenji; Takahashi, Johji; Oguchi, Katsuji; Masuda, Yutaka; Hara, Hajime; Usami, Shino; Kiuchi, Yuji

2012-04-01

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

MTHFR Gene Polymorphism-Mutations and Air Pollution as Risk Factors for Breast Cancer: A Metaprediction Study.

PubMed

Gonzales, Mildred C; Yu, Pojui; Shiao, S Pamela K

The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations.

Association between tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis.

PubMed

Ma, Liping; Zhao, Jiangyang; Li, Taijie; He, Yu; Wang, Jian; Xie, Li; Qin, Xue; Li, Shan

2014-03-25

Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-α gene, -308G/A and -238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis. We conducted a comprehensive literature search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature database (CBM), and the China National Knowledge Infrastructure (CNKI). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI). In this meta-analysis, we included 14 studies with 5,757 patients and 6,137 control subjects for the TNF-α-308G/A polymorphism and 1,967 patients and 2,004 control subjects for the TNF-α-238C/T polymorphism. A significantly increased prostate cancer risk was found to be associated with the TNF-α-308C/T polymorphism in studies with healthy volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093-2.145; P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047-2.085; P = 0.026). No significant association was found between the TNF-α-238G/A polymorphism and prostate cancer risk in the overall or subgroup analyses. There was no risk of publication bias in this meta-analysis. Our results suggest that while the TNF-α-238G/A polymorphism may not be associated with prostate cancer the TNF-α-308C/T polymorphism may significantly contribute to prostate cancer susceptibility in healthy volunteers. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1629288120116301.

Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis.

PubMed

Naranjo-Galvis, C A; de-la-Torre, A; Mantilla-Muriel, L E; Beltrán-Angarita, L; Elcoroaristizabal-Martín, X; McLeod, R; Alliey-Rodriguez, N; Begeman, I J; López de Mesa, C; Gómez-Marín, J E; Sepúlveda-Arias, J C

2018-04-01

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii , which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the "dideoxynucleotide (ddNTP) primer extension" technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (-1082G/A) was significantly more prevalent in OT patients than in controls ( P = 1.93e-08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e-07). In contrast, haplotype "AG" of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients ( P = 7e-04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT ( P = 3.37e-05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e-04). Haplotype "GAG" of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT ( P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population. Copyright © 2018 American Society for Microbiology.

Genetic polymorphisms within tumor necrosis factor gene promoter region: a role for susceptibility to ventilator-associated pneumonia.

PubMed

Kotsaki, Antigoni; Raftogiannis, Maria; Routsi, Christina; Baziaka, Fotini; Kotanidou, Anastasia; Antonopoulou, Anastasia; Orfanos, Stylianos E; Katsenos, Chrisostomos; Koutoukas, Pantelis; Plachouras, Diamantis; Mandragos, Konstantinos; Giamarellos-Bourboulis, Evangelos J

2012-08-01

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at the -376, -308 and -238 position of the promoter region of the TNF gene were assessed by restriction fragment length polymorphisms. Monocytes were isolated from 47 patients when they developed sepsis and stimulated by bacterial endotoxin for the production of TNFα and of interleukin-6 (IL-6). Patients were divided into two groups; 166 patients bearing only wild-type alleles of all three studied polymorphisms; and 47 patients carrying at least one A allele of the three studied SNPs. Time between start of mechanical ventilation and advent of VAP was significantly shorter in the second group than in the first group (log-rank: 4.416, p: 0.041). When VAP supervened, disease severity did not differ between groups. Stimulation of TNFα and of IL-6 was much greater by monocytes for patients carrying A alleles. Carriage of at least one A allele of the three studied SNPs at the promoter region of the TNF-gene is associated with shorter time to development of VAP but it is not associated with disease severity. Findings may be related with a role of the studied SNPs in the production of pro-inflammatory cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymorphisms of the tumor necrosis factor-alpha receptor 2 gene are associated with obesity phenotypes among 405 Caucasian nuclear families.

PubMed

Zhao, Lan-Juan; Xiong, Dong-Hai; Pan, Feng; Liu, Xiao-Gang; Recker, Robert R; Deng, Hong-Wen

2008-09-01

The plasma level of the tumor necrosis factor-alpha receptor 2 (TNFR2) is associated with obesity phenotypes. However, the genetic polymorphisms for such an association have rarely been explored and are generally unknown. In this study, by employing a large sample of 1,873 subjects from 405 Caucasian nuclear families, we explored the association of 12 SNPs of the TNFR2 gene and obesity-related phenotypes, including body mass index (BMI), fat mass, and percentage fat mass (PFM). The within-family quantitative transmission disequilibrium test, which is robust to sample stratification, was implemented to evaluate the association of TNFR2 gene with obesity phenotypes. Evidence of association was obtained at SNP9 (rs5746059) with fat mass (P = 0.0002), BMI (P = 0.002), and PFM (P = 0.0006). The contribution of this polymorphism to the variation of fat mass and PFM was 6.24 and 7.82%, respectively. Individuals carrying allele A at the SNP9 site had a 4.6% higher fat mass and a 2.5% increased PFM compared to noncarriers. The results remained significant even after correction for multiple testing. Evidence of association between the TNFR2 gene and obesity phenotypes are also found in 700 independent Chinese Han and 1,000 random Caucasians samples. The results suggest that the TNFR2 gene polymorphisms contribute to the variation of obesity phenotypes.

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.

TGF-β Polymorphisms Are a Risk Factor for Chagas Disease

PubMed Central

Ferreira, Roberto Rodrigues; Madeira, Fabiana da Silva; Alves, Gabriel Farias; Chambela, Mayara da Costa; Curvo, Eduardo de Oliveira Vaz; Moreira, Aline dos Santos; Almeida de Sá, Renata; Cabello, Pedro Hernan; Bailly, Sabine; Araujo-Jorge, Tania Cremonini; Saraiva, Roberto Magalhães

2018-01-01

Transforming growth factor β1 (TGF-β1) is an important mediator in Chagas disease. Furthermore, patients with higher TGF-β1 serum levels show a worse clinical outcome. Gene polymorphism may account for differences in cytokine production during infectious diseases. We tested whether TGFB1 polymorphisms could be associated with Chagas disease susceptibility and severity in a Brazilian population. We investigated five single-nucleotide polymorphisms (−800 G>A, −509 C>T, +10 T>C, +25 G>C, and +263 C>T). 152 patients with Chagas disease (53 with the indeterminate form and 99 with the cardiac form) and 48 noninfected subjects were included. Genotypes CT and TT at position −509 of the TGFB1 gene were more frequent in Chagas disease patients than in noninfected subjects. Genotypes TC and CC at codon +10 of the TGFB1 gene were also more frequent in Chagas disease patients than in noninfected subjects. We found no significant differences in the distribution of the studied TGFB1 polymorphisms between patients with the indeterminate or cardiac form of Chagas disease. Therefore, −509 C>T and +10 T>C TGFB1 polymorphisms are associated with Chagas disease susceptibility in a Brazilian population. PMID:29670670

Functional polymorphisms in the sigma1 receptor gene associated with alcoholism.

PubMed

Miyatake, Ryosuke; Furukawa, Aizo; Matsushita, Sachio; Higuchi, Susumu; Suwaki, Hiroshi

2004-01-01

Sigma1 receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study. We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects. A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi2=5.575, df=1, p=.0205) and the TT-241-240/Pro2 haplotype (chi2=21.464, df=1, p<.0001) were significantly higher in control subjects compared with alcoholic subjects. The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism.

No association between polymorphisms/haplotypes of the vascular endothelial growth factor gene and preeclampsia

PubMed Central

2011-01-01

Background Preeclampsia (PE) is the first worldwide cause of death in pregnant women, intra-uterine growth retardation, and fetal prematurity. Some vascular endothelial grown factor gene (VEGF) polymorphisms have been associated to PE and other pregnancy disturbances. We evaluated the associations between VEGF genotypes/haplotypes and PE in Mexican women. Methods 164 pregnant women were enrolled in a case-control study (78 cases and 86 normotensive pregnant controls). The rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (+405G/C), and rs25648 (-7C/T), VEGF variants were discriminated using Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) methods or Taqman single nucleotide polymorphism (SNP) assays. Results The proportions of the minor allele for rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs were 0.33, 0.2, 0.39, and 0.17 in controls, and 0.39, 0.23, 0.41, and 0.15 in cases, respectively (P values > 0.05). The most frequent haplotypes of rs699947, rs1570360, rs2010963, and rs25648 VEGF SNPs, were C-G-C-C and C-G-G-C with frequencies of 0.39, 0.21 in cases and 0.37, 0.25 in controls, respectively (P values > 0.05) Conclusion There was no evidence of an association between VEGF alleles, genotypes, or haplotypes frequencies and PE in our study. PMID:21575227

PD-1 gene polymorphism in children with subacute sclerosing panencephalitis.

PubMed

Piskin, Ibrahim Etem; Calık, Mustafa; Abuhandan, Mahmut; Kolsal, Ebru; Celik, Sevim Karakas; Iscan, Akın

2013-08-01

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory and degenerative disorder of the central nervous system. Several factors influence the risk of chronic brain infection with the mutant measles virus. However, to date, no pathogenic mechanism that may predispose to SSPE has been determined. Studies have indicated that specific polymorphisms in certain host genes are probably involved in impairing the ability of host immune cells to eradicate the measles virus in SSPE patients. Programmed cell death protein 1 (PD-1), a member of the CD28 family, is a negative regulator of the immune system. The purpose of our study was to investigate whether PD-1 gene polymorphisms affect susceptibility to the development of SSPE in Turkish children. In total, 109 subjects (54 SSPE patients and 55 healthy controls) were genotyped for the PD-1.9 C/T (rs2227982) single-nucleotide polymorphism (SNP). The distributions of T alleles in the PD-1.9 polymorphism in SSPE patients and healthy controls were 2.8 and 10.9%, respectively. There was a statistically significant difference between the groups; the 95% confidence interval (CI) was 0.06 to 0.85 and the odds ratio (OR) was 0.23 (χ(2) test). Thus, we identified an association between SSPE and the PD-1 rs2227982 gene polymorphism; the frequency of T alleles was higher in controls than in SSPE patients. Georg Thieme Verlag KG Stuttgart · New York.

[Liver cirrhosis patogenetics: polymorphism of glutation S-transferase genes].

PubMed

Goncharova, I A; Rachkovskiĭ, M I; Beloborodova, E V; Gamal' Abd El'-Aziz Nasar, Kh; Puzyrev, V P

2010-01-01

Association of deletion polymorphism in GSTT1 and GSTM1 genes and polymorphic variant A313G of GSTP1 gene with cirrhosis diseases and 4-year survival rate for the Tomsk region (West Siberia) patients were tested. Homozygous deletion of GSTM1 gene (null genotype) was a protective factor for alcoholic and mixed (HCV, HBV and alcohol) liver cirrhosis development. The patients from the joint group (all etiology forms) as well as having alcoholic and mixed cirrhosis had lower frequency of GSTM1 null genotype (39.2, 39.0, and 34.2%, respectively) in comparison with the control group (64.6%). The GSTM1 null genotype and GSTP1 gene A313G polymorphic variant correlated with the patients' survival rate. The patients survived in comparison with the dead had higher frequency of a GSTM1 null genotype (46.6 vs. 30.2%) and GSTP1 AA genotype (63.1 vs. 40.5%), and lower frequency of GSTP1 AG (A313G) genotype (31.1 vs. 51.2%). A survival rate was 2.5 times higher for patients having GSTP1 AA genotype in comparison with the GG and AG genotype carriers and 2 times higher for patients having GSTM1 null genotype than the gene carriers. A 4-year fatal case probability was 2.3 times higher among the patients having heterozygous AG GSTP1 genotype in comparison with homozygous AA and GG genotype carriers.

Polymorphisms of the TLR4 gene and risk of gastric cancer.

PubMed

Huang, Lina; Yuan, Kexin; Liu, Jingjing; Ren, Xiyun; Dong, Xiaoqun; Tian, Wenjing; Jia, Yunhe

2014-03-01

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene-environmental interactions on the risk of GC in Northeastern China. We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models. Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR=0.33, 95% CI 0.18-0.60, P<0.001 and adjusted OR=0.37, 95% CI 0.21-0.67, P=0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC. Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC. Copyright © 2013 Elsevier B.V. All rights reserved.

Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression: The NewGeneris Cohort

PubMed Central

Merlo, Domenico Franco; Agramunt, Silvia; Anna, Lívia; Besselink, Harrie; Botsivali, Maria; Brady, Nigel J.; Ceppi, Marcello; Chatzi, Leda; Chen, Bowang; Decordier, Ilse; Farmer, Peter B.; Fleming, Sarah; Fontana, Vincenzo; Försti, Asta; Fthenou, Eleni; Gallo, Fabio; Georgiadis, Panagiotis; Gmuender, Hans; Godschalk, Roger W.; Granum, Berit; Hardie, Laura J.; Hemminki, Kari; Hochstenbach, Kevin; Knudsen, Lisbeth E.; Kogevinas, Manolis; Kovács, Katalin; Kyrtopoulos, Soterios A.; Løvik, Martinus; Nielsen, Jeanette K; Nygaard, Unni Cecilie; Pedersen, Marie; Rydberg, Per; Schoket, Bernadette; Segerbäck, Dan; Singh, Rajinder; Sunyer, Jordi; Törnqvist, Margareta; van Loveren, Henk; van Schooten, Frederik J.; Vande Loock, Kim; von Stedingk, Hans; Wright, John; Kirsch-Volders, Micheline; van Delft, Joost H.M.

2013-01-01

Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure–outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG–DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN

Interactions among insulin resistance, inflammation factors, obesity-related gene polymorphisms, environmental risk factors, and diet in the development of gestational diabetes mellitus.

PubMed

Feng, Yang; Jiang, Chen-Dong; Chang, Ai-Min; Shi, Ying; Gao, Junjun; Zhu, Linlin; Zhang, Zhan

2018-03-08

The aim of this study was to investigate the correlations and interactions between the polymorphisms of insulin resistance-related genes (ADIPOQ rs2241766), inflammation factors (TNF-α rs1800629, IL-6 rs1800795), obesity-related genes (GNB3 rs5443, ADRB rs1042714), and risk factors for gestational diabetes mellitus (GDM) such as diet structure in the development of GDM. This research was conducted among women who visited the third-affiliate hospital of Zhengzhou University for pregnancy checkups from 1 June 2014 to 30 December 2014. Based on the results of a 75-g glucose tolerance test (OGTT), 140 pregnant women with GDM were randomly selected as a part of the GDM group and140 healthy, pregnant women as part of the control group. Relevant clinical and laboratory data for the child and the mother including her pregnancy outcomes and the delivery mode were collected for the epidemiological survey. The results showed that risk factors for GDM are advanced age, the hepatitis B virus, family history of diabetes, high body mass index before pregnancy, and weight gain of ≥10 kg before 24-week gestation. We found that diet structures were severely unbalanced. The polymorphisms rs2241766 and rs5443 were found to potentially be associated with GDM; moreover, a positive interaction was demonstrated between rs2241766 and age, and a negative interaction was demonstrated with weight gain of ≥10 kg before 24-week gestation. Our findings demonstrate that both environmental risk factors and genetic background contribute to the development of GDM.

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

PubMed

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Effect of the g.-723G-->T polymorphism in the bovine myogenic factor 5 (Myf5) gene promoter region on gene transcript level in the longissimus dorsi muscle and on meat traits of Polish Holstein-Friesian cattle.

PubMed

Robakowska-Hyzorek, Dagmara; Oprzadek, Jolanta; Zelazowska, Beata; Olbromski, Rafał; Zwierzchowski, Lech

2010-06-01

Myogenic factor 5 (Myf5), a product of the Myf5 gene, belongs to the MRF family of basic helix-loop-helix transcription factors that regulate myogenesis. Their roles in muscle growth and development make their genes candidates for molecular markers of meat production in livestock, but nucleotide sequence polymorphism has not been thoroughly studied in MRF genes. We detected four single nucleotide polymorphisms (SNPs) within exon 1 of the Myf5 gene, encoding the NH-terminal transactivation domain of the Myf5 protein. Three of these mutations change the amino acid sequence. The distribution of these SNPs was highly skewed in cattle populations; most of the mutations were found in only a few or even single individuals. Of the nine SNPs found in the promoter region of Myf5, one (transversion g.-723G-->T) was represented by all three genotypes distributed in the cattle populations studied. This polymorphism showed an influence on Myf5 gene expression in the longissimus dorsi muscle and was associated with sirloin weight and fat weight in sirloin in carcasses of Holstein-Friesian cattle.

Tumour necrosis factor-alpha polymorphism as one of the complex inherited factors in pemphigus.

PubMed Central

Torzecka, Jolanta Dorota; Narbutt, Joanna; Sysa-Jedrzejowska, Anna; Borowiec, Maciej; Ptasinska, Anetta; Woszczek, Grzegorz; Kowalski, Marek L

2003-01-01

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus. PMID:14760938

Tumour necrosis factor-alpha polymorphism as one of the complex inherited factors in pemphigus.

PubMed

Torzecka, Jolanta Dorota; Narbutt, Joanna; Sysa-Jedrzejowska, Anna; Borowiec, Maciej; Ptasinska, Anetta; Woszczek, Grzegorz; Kowalski, Marek L

2003-10-01

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-alpha promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-alpha gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls. Carriers of the TNF-alpha polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR) = 8.12; p = 0.0005). A significant association between HLA-DRB1*04 (OR = 3.86; pcor = 0.0001) and DRB1*14 (OR = 8.4; pcor = 0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR = 0.08; pcor = 0.006) was also identified. We have shown for the first time a positive association of TNF-alpha polymorphism in position -308 with pemphigus foliaceus.

Gene Presence-Absence Polymorphism in Castrating Anther-Smut Fungi: Recent Gene Gains and Phylogeographic Structure.

PubMed

Hartmann, Fanny E; Rodríguez de la Vega, Ricardo C; Brandenburg, Jean-Tristan; Carpentier, Fantin; Giraud, Tatiana

2018-04-01

Gene presence-absence polymorphisms segregating within species are a significant source of genetic variation but have been little investigated to date in natural populations. In plant pathogens, the gain or loss of genes encoding proteins interacting directly with the host, such as secreted proteins, probably plays an important role in coevolution and local adaptation. We investigated gene presence-absence polymorphism in populations of two closely related species of castrating anther-smut fungi, Microbotryum lychnidis-dioicae (MvSl) and M. silenes-dioicae (MvSd), from across Europe, on the basis of Illumina genome sequencing data and high-quality genome references. We observed presence-absence polymorphism for 186 autosomal genes (2% of all genes) in MvSl, and only 51 autosomal genes in MvSd. Distinct genes displayed presence-absence polymorphism in the two species. Genes displaying presence-absence polymorphism were frequently located in subtelomeric and centromeric regions and close to repetitive elements, and comparison with outgroups indicated that most were present in a single species, being recently acquired through duplications in multiple-gene families. Gene presence-absence polymorphism in MvSl showed a phylogeographic structure corresponding to clusters detected based on SNPs. In addition, gene absence alleles were rare within species and skewed toward low-frequency variants. These findings are consistent with a deleterious or neutral effect for most gene presence-absence polymorphism. Some of the observed gene loss and gain events may however be adaptive, as suggested by the putative functions of the corresponding encoded proteins (e.g., secreted proteins) or their localization within previously identified selective sweeps. The adaptive roles in plant and anther-smut fungi interactions of candidate genes however need to be experimentally tested in future studies.

Gene Presence–Absence Polymorphism in Castrating Anther-Smut Fungi: Recent Gene Gains and Phylogeographic Structure

PubMed Central

Rodríguez de la Vega, Ricardo C; Brandenburg, Jean-Tristan; Carpentier, Fantin; Giraud, Tatiana

2018-01-01

Abstract Gene presence–absence polymorphisms segregating within species are a significant source of genetic variation but have been little investigated to date in natural populations. In plant pathogens, the gain or loss of genes encoding proteins interacting directly with the host, such as secreted proteins, probably plays an important role in coevolution and local adaptation. We investigated gene presence–absence polymorphism in populations of two closely related species of castrating anther-smut fungi, Microbotryum lychnidis-dioicae (MvSl) and M. silenes-dioicae (MvSd), from across Europe, on the basis of Illumina genome sequencing data and high-quality genome references. We observed presence–absence polymorphism for 186 autosomal genes (2% of all genes) in MvSl, and only 51 autosomal genes in MvSd. Distinct genes displayed presence–absence polymorphism in the two species. Genes displaying presence–absence polymorphism were frequently located in subtelomeric and centromeric regions and close to repetitive elements, and comparison with outgroups indicated that most were present in a single species, being recently acquired through duplications in multiple-gene families. Gene presence–absence polymorphism in MvSl showed a phylogeographic structure corresponding to clusters detected based on SNPs. In addition, gene absence alleles were rare within species and skewed toward low-frequency variants. These findings are consistent with a deleterious or neutral effect for most gene presence–absence polymorphism. Some of the observed gene loss and gain events may however be adaptive, as suggested by the putative functions of the corresponding encoded proteins (e.g., secreted proteins) or their localization within previously identified selective sweeps. The adaptive roles in plant and anther-smut fungi interactions of candidate genes however need to be experimentally tested in future studies. PMID:29722826

Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

PubMed

Negi, Vir S; Devaraju, Panneer; Gulati, Reena

2015-09-01

SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian

Estrogen Receptor 1 ( ESR1) Gene Polymorphisms and Obesity Phenotypes in a Population of Young Adults.

PubMed

Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; González-Jiménez, Emilio; Rueda-Medina, Blanca

2017-06-01

Obesity is considered an increasingly serious health problem determined by multiple genetic and environmental factors. Estrogens have been found to play a major role in body weight and adiposity regulation through estrogen receptor 1 ( ESR1). The aim of this study was to determine whether genotype and haplotype frequencies of ESR1 polymorphisms are associated with body composition measures in a population of 572 young adults. A lack of significant association between genotypes of ESR1 gene polymorphisms and obesity phenotypes was seen after adjustment for confounding factors. Linkage disequilibrium (LD) analysis identified a single LD block for the ESR1 gene including PvuII and XbaI single-nucleotide polymorphisms (SNPs) (pairwise r 2 = .66). None of the haplotypes identified revealed statistically significant associations with any of the obesity phenotypes. Our results suggest that polymorphisms of the ESR1 gene do not contribute significantly to the genetic risk for obesity phenotypes in a population of young Caucasian adults.

The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

PubMed

Kinoshita, Yumiko; Kizaki, Zenro; Ishihara, Yasunori; Nakajima, Hisakazu; Adachi, Shinsuke; Kosaka, Kitaro; Kinugasa, Akihiko; Sugimoto, Tohru

2007-01-01

Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p < 0.05) and no significant for premature birth, short-birth height and low-birth weight. This is the first study showing the role of the promoter region of the IGF-I gene polymorphism and the level of plasma IGF-I and body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

PubMed

Damberg, M; Garpenstrand, H; Alfredsson, J; Ekblom, J; Forslund, K; Rylander, G; Oreland, L

2000-03-01

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island.

PubMed

Sousa, Ana Célia; Palma Dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

2017-10-01

Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results.The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island.A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions.In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology.

Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension in Madeira Island

PubMed Central

Sousa, Ana Célia; Palma dos Reis, Roberto; Pereira, Andreia; Borges, Sofia; Freitas, Ana Isabel; Guerra, Graça; Góis, Teresa; Rodrigues, Mariana; Henriques, Eva; Freitas, Sónia; Ornelas, Ilídio; Pereira, Décio; Brehm, António; Mendonça, Maria Isabel

2017-01-01

Abstract Essential hypertension (EH) is a complex disease in which physiological, environmental, and genetic factors are involved in its genesis. The genetic variant of the alpha-adducin gene (ADD1) has been described as a risk factor for EH, but with controversial results. The objective of this study was to evaluate the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a population from Madeira Island. A case-control study with 1614 individuals of Caucasian origin was performed, including 817 individuals with EH and 797 controls. Cases and controls were matched for sex and age, by frequency-matching method. All participants collected blood for biochemical and genotypic analysis for the Gly460Trp polymorphism. We further investigated which variables were independently associated to EH, and, consequently, analyzed their interactions. In our study, we found a significant association between the ADD1 gene polymorphism and EH (odds ratio 2.484, P = .01). This association remained statistically significant after the multivariate analysis (odds ratio 2.548, P = .02). The ADD1 Gly460Trp gene polymorphism is significantly and independently associated with EH risk in our population. The knowledge of genetic polymorphisms associated with EH is of paramount importance because it leads to a better understanding of the etiology and pathophysiology of this pathology. PMID:29049185

Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: the NewGeneris cohort.

PubMed

Merlo, Domenico Franco; Agramunt, Silvia; Anna, Lívia; Besselink, Harrie; Botsivali, Maria; Brady, Nigel J; Ceppi, Marcello; Chatzi, Leda; Chen, Bowang; Decordier, Ilse; Farmer, Peter B; Fleming, Sarah; Fontana, Vincenzo; Försti, Asta; Fthenou, Eleni; Gallo, Fabio; Georgiadis, Panagiotis; Gmuender, Hans; Godschalk, Roger W; Granum, Berit; Hardie, Laura J; Hemminki, Kari; Hochstenbach, Kevin; Knudsen, Lisbeth E; Kogevinas, Manolis; Kovács, Katalin; Kyrtopoulos, Soterios A; Løvik, Martinus; Nielsen, Jeanette K; Nygaard, Unni Cecilie; Pedersen, Marie; Rydberg, Per; Schoket, Bernadette; Segerbäck, Dan; Singh, Rajinder; Sunyer, Jordi; Törnqvist, Margareta; van Loveren, Henk; van Schooten, Frederik J; Vande Loock, Kim; von Stedingk, Hans; Wright, John; Kleinjans, Jos C; Kirsch-Volders, Micheline; van Delft, Joost H M

2014-02-01

Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1

Selection with Gene-Cytoplasm Interactions. I. Maintenance of Cytoplasm Polymorphisms

PubMed Central

Gregorius, H. R.; Ross, M. D.

1984-01-01

General conditions for the protectedness of gene-cytoplasm polymorphisms are considered for a biallelic model with two cytoplasm types and under the assumption that nuclear polymorphisms cannot be maintained in the presence of only one cytoplasm type. Analytical results involving male fertilities, female fertilities, viabilities and selfing rates are obtained, and numerical results show spiral and cyclic behavior of population trajectories. It is shown that a maternally inherited cytoplasmic polymorphism cannot be maintained in the absence of a nuclear polymorphism, and that a gene-cytoplasm polymorphism can only be maintained if the population shows sexual asymmetry, i.e. , if the ratio of male to female fertility varies among genotypes. Thus, the classical viability selection model does not allow gene-cytoplasm polymorphisms. PMID:17246213

Leptin gene and leptin receptor gene polymorphisms are associated with sweet preference and obesity.

PubMed

Mizuta, Einosuke; Kokubo, Yoshihiro; Yamanaka, Itaru; Miyamoto, Yoshihiro; Okayama, Akira; Yoshimasa, Yasunao; Tomoike, Hitonobu; Morisaki, Hiroko; Morisaki, Takayuki

2008-06-01

Leptin is an adipocyte-secreted hormone that regulates food intake and body weight, and that was recently reported to suppress sweet sensitivity in an animal model. We investigated the associations among sweet preference, obesity, and polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of 3,653 residents randomly selected from among the citizens of Suita City, Osaka, Japan were enlisted as subjects, in whom we investigated sweet preference, clinical characteristics, including obesity and serum leptin level, and the polymorphisms of LEP and LEPR (G-2548A and A19G for LEP; R109K, R223Q, and rs3790439 for LEPR). We determined the associations among the parameters using logistic regression analysis, in order to consider potential confounding factors for sweet preference and/or obesity. The LEP A19G and LEPR R109K polymorphisms were associated with sweet preference, whereas the serum leptin level was not. Further, the LEPR 109KK genotype was found to be associated with obesity along with sweet preference. In conclusion, our results are the first to show associations of LEP and LEPR polymorphisms with sweet preference, and may provide useful information for diagnosis and treatment of lifestyle-related diseases.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

PubMed

Adole, Prashant S; Kharbanda, Parampreet S; Sharma, Sadhna

2016-05-01

Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

PubMed Central

Adole, Prashant S.; Kharbanda, Parampreet S.; Sharma, Sadhna

2016-01-01

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures. PMID:27488001

Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.

PubMed

Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

2008-05-01

The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls. A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34). To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

PubMed

Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Amid, Reza; Youssefi, Navid; Mehdizadeh, Amir Reza

2013-07-13

Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576) with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to 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. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant). There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239). Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239). The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

PubMed

Pietrowski, Detlef; Bettendorf, Herta; Keck, Christoph; Bürkle, Bernd; Unfried, Gertrud; Riener, Eva-Katrin; Hefler, Lukas A; Tempfer, Clemens

2004-02-01

The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients.

PubMed

Gutierrez-Rubio, S A; Quintero-Ramos, A; Durán-Cárdenas, A; Franco-Topete, R A; Castro-Cervantes, J M; Oceguera-Villanueva, A; Jiménez-Pérez, L M; Balderas-Peña, L M A; Morgan-Villela, G; Del-Toro-Arreola, A; Daneri-Navarro, A

2015-02-13

MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

Association of I-FABP gene polymorphism and the risk of coronary heart disease.

PubMed

Yuan, Dong; Yu, Changqing; Zeng, Chunyu

2015-01-01

The study aimed to investigate the association between polymorphism of I-FABP gene and coronary heart disease (CHD). 225 patients with CHD were randomly recruited into the case group, and 196 healthy elderly volunteers were recruited from Medical Examination Center of our hospital as control. General clinical data were collected and plasma TC, TG, LDL-C, HDL-C levels were measured. Besides, polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technology were used to detect the polymorphism of Hha-I enzyme cleavage sites in I-FABP gene in the study population. Hha-I cleavage sites occurred at codon 54 in exon in the coding sequencing of I-FABP gene in all participants. After cleavage with Hha-I enzyme, the genotypes were identified as wild-type A/A, heterozygous mutant A/T and homozygous mutant T/T. In case group, A/T and T/T genetic carriers had significantly higher levels of TC, TG and LDL-C than A/A carriers (P<0.05). However, in control group, similar differences were not observed (P>0.05). BMI, dietary habits and I-FABP alleles were independent risk factors of CHD. The polymorphism of I-FABP gene existed in the study population. And this genetic variation had influence on lipid metabolism, which was associated with the risk of developing CHD. I-FABP gene polymorphism may contribute to the increased genetic susceptibility to CHD.

Glutathione S-transferase (GSTM1, GSTT1) gene polymorphisms, maternal gestational weight gain, bioimpedance factors and their relationship with birth weight: a cross-sectional study in Romanian mothers and their newborns.

PubMed

Mărginean, Claudiu; Bănescu, Claudia Violeta; Mărginean, Cristina Oana; Tripon, Florin; Meliţ, Lorena Elena; Iancu, Mihaela

2017-01-01

The aim of this study was to assess the relationship between mother-child GSTM1, GSTT1 gene polymorphisms, maternal weight gain, maternal bioimpedance parameters and newborn's weight, in order to identify the factors that influence birth weight. We performed a cross-sectional study on 405 mothers and their newborns, evaluated in an Obstetrics and Gynecology Tertiary Hospital from Romania. Newborns whose mothers had the null genotype of GSTT1 gene polymorphism were more likely to gain a birth weight of >3 kg, compared to newborns whose mothers had the T1 genotype (odds ratio - OR: 2.14, 95% confidence interval - CI: [1.03; 4.44]). Also, the null genotype of GSTM1 gene polymorphism in both mothers and newborns was associated with a higher birth weight. Gestational weight gain was positively associated with newborn's birth weight (p<0.001). The increased mother's fat mass (%) and basal metabolism rate were also independent factors for a birth weight of more than 3 kg (p=0.006 and p=0.037). The null genotype of GSTT1 gene polymorphism in mothers and the null genotype of GSTM1 in mothers and newborns had a positive effect on birth weight. Also, increased maternal fat mass and basal metabolism rate were associated with increased birth weight. We conclude that maternal GSTM1÷GSTT1 gene polymorphisms present an impact on birth weight, being involved in the neonatal nutritional status. The clinical relevance of our study is sustained by the importance of identifying the factors that influence birth weight, which can be triggers for childhood obesity.

HOTAIR gene polymorphisms contribute to increased neuroblastoma susceptibility in Chinese children.

PubMed

Yang, Xu; He, Jing; Chang, Yitian; Luo, Annie; Luo, Ailing; Zhang, Jiao; Zhang, Ruizhong; Xia, Huimin; Xu, Ling

2018-06-15

Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. Previous studies have shown that single-nucleotide polymorphisms in some genes are associated with the risk of multiple cancers, including neuroblastoma. Although Hox transcript antisense intergenic RNA (HOTAIR) gene polymorphisms have been investigated in a variety of cancers, to the authors' knowledge the relationships between HOTAIR gene polymorphisms and neuroblastoma susceptibility have not been reported to date. The objective of the current study was to evaluate the correlation between HOTAIR gene polymorphisms and neuroblastoma risk in Chinese children. The authors genotyped 6 polymorphisms (rs920778 A>G, rs12826786 C>T, rs4759314 A>G, rs7958904 G>C, rs874945 C>T, and rs1899663 C>A) of the HOTAIR gene in 2 Chinese populations including 393 neuroblastoma cases and 812 healthy controls. The strength of the associations was evaluated using odds ratios and 95% confidence intervals. Further stratification analyses were conducted to explore the association between the HOTAIR gene polymorphisms rs12826786 C>T, rs874945 C>T, and rs1899663 C>A with neuroblastoma susceptibility in terms of age, sex, clinical stage of disease, and sites of origin. The authors found that the rs12826786 C>T (P =.013), rs874945 C>T (P =.020), and rs1899663 C>A (P =.029) polymorphisms were significantly associated with increased neuroblastoma risk. In stratification analyses, these associations were more predominant in females and among patients with tumor in the retroperitoneal region or mediastinum. The remaining 3 polymorphisms were not found to be related to neuroblastoma susceptibility. The results of the current study verified that HOTAIR gene polymorphisms are associated with increased neuroblastoma risk and suggest that HOTAIR gene polymorphisms might be a potential biomarker for neuroblastoma susceptibility. Cancer 2018;124:2599-606. © 2018 American Cancer Society. © 2018 American Cancer Society.

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

PubMed

Podgoreanu, M V; White, W D; Morris, R W; Mathew, J P; Stafford-Smith, M; Welsby, I J; Grocott, H P; Milano, C A; Newman, M F; Schwinn, D A

2006-07-04

The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population.

PubMed

Kong, Fanjun; Liu, Jie; Liu, Yongheng; Song, Bao; Wang, Hualing; Liu, Wenchao

2010-06-17

Interleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP). There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P = 0.041) and larger tumor size (P = 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022) and higher tumor stage(p = 0.028) of breast cancer at the time of diagnosis compared with others. Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and coagulation factor VII Arg353-->Gln polymorphism in Korean patients with coronary artery disease.

PubMed Central

Song, J.; Yoon, Y. M.; Jung, H. J.; Hong, S. H.; Park, H.; Kim, J. Q.

2000-01-01

An increased risk for arterial thrombosis is associated with high plasma levels of coagulation and fibrinolytic factors such as PAI-1 and FVII. In this study, the 4G/5G polymorphism in the promoter of PAI-1 gene and Arg353-->Gln polymorphism in the FVII gene were analysed in 139 normal adults and 158 patients with coronary artery disease (CAD), and their association with plasma lipid traits was investigated. There were no significant differences in the allele frequencies of PAI-1 and FVII polymorphisms between control and patient groups. The allelic distributions of both polymorphisms in Koreans were similar to those in Japanese but significantly different from those in Caucasians. In the CAD group, the 4G homozygotes of PAI-1 polymorphism showed significantly higher levels of total (p=0.0250) and LDL cholesterol (p=0.0335) with individuals having other genotypes. However, FVII polymorphism showed no association with lipid levels. In conclusion, the 4G/5G PAI-1 promoter polymorphism and Arg353-->Gln FVII polymorphism are not major genetic risk factors for CAD in Koreans. However, 4G allele of PAI-1 polymorphism revealed to be associated with the levels of cholesterol, especially LDL cholesterol levels in CAD patients. PMID:10803689

Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease.

PubMed

Abd El-Aziz, Tarek A; Mohamed, Rasha H

2013-12-15

The aim of this study was to investigate the association between C-reactive protein (CRP) gene polymorphism and metabolic syndrome (MetS) with premature coronary artery disease (PCAD). 116 patients with PCAD (58 with MetS and 58 without MetS) and 119 controls were included in the study. CRP gene +1059 G>C polymorphism was analyzed by polymerase chain reaction. Serum hs-CRP was measured using high-sensitivity enzyme-linked immunosorbent assay. Carriers of C allele of the CRP +1059 G>C polymorphism had 3.37 fold increased risk to develop MetS in patients with PCAD. In addition CRP gene and hs-CRP levels were independent risk factors for PCAD and MetS. The present study provides new evidence that the presence of CRP +1059 G>C polymorphism and hs-CRP levels are independent determinants of PCAD and MetS in Egyptians. The results of our study suggest a synergistic effect of CRP C allele with classical risk factors such as hypertension, obesity, dyslipidemia and MetS. © 2013 Elsevier B.V. All rights reserved.

Gene polymorphisms of tumor necrosis factor alpha-308 and interleukin-10-1082 among asthmatic Egyptian children.

PubMed

Zedan, Magdy; Settin, Ahmed; Farag, Mohammad K; El-Bayoumi, Mohammed; El Regal, Mohammed Ezz; El Baz, Rizk; Osman, Engy

2008-01-01

Tumor necrosis factor (TNF) alpha-308 and interleukin (IL)-10(-1082) have potent inflammatory responses in the process of airway inflammation in asthma. The purpose of this study was to check for association of polymorphisms related to cytokine genes with susceptibility and severity of bronchial asthma in Egyptian children. Blood samples of 69 asthmatic children receiving treatment and follow-up at the Allergy and Respiratory Medicine Unit, Mansoura University Children Hospital, Mansoura, Egypt, were subjected to DNA extraction and amplification using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms in the promoter regions of cytokine genes TNF-alpha(-308(G-->A)), IL-10(-1082(G-->A)). Compared with normal controls, Egyptian asthmatic children showed a significant higher frequency of IL-10(-1082) G/G homozygosity genotype (p < 0.001; odds ratio [OR] = 7) with lower frequency of G/A heterozygosity genotype among cases. This finding also was detected in cases with persistent asthma and eczema. These cases showed significant lower frequency of TNF-alpha-308 G/A heterozygosity (p < 0.05; OR = 0.44). Also, male cases, cases with positive family history, and those patients with persistent types of asthma showed a higher frequency of TNF-alpha-308 G/G homozygosity. IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G may be a contributing factor in susceptibility as well as severity of asthma among Egyptian children. Separate studies should be specified relating these cytokine genotypes to response to various modalities in asthma therapy. This study reports that IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G genotypes may be contributing factors in susceptibility as well as in severity of asthma among Egyptian children. Separate studies may be specified relating these cytokine genotypes to response to various modalities in asthma therapy.

Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor-1 polymorphism 4G/5G and the risk of retinal vein occlusion.

PubMed

Kuhli-Hattenbach, Claudia; Hellstern, Peter; Nägler, Dorit Karin; Kohnen, Thomas; Hattenbach, Lars-Olof

2017-01-01

Thus far, no data has become available to evaluate systematically the prevalences of prothrombin polymorphism A19911G (PT A19911G), factor V HR2 haplotype A4070G (FV A4070G), or plasminogen activator-inhibitor-1 polymorphism 4G/5G (PAI-1 4G/5G) in patients who develop retinal vein occlusion (RVO) without cardiovascular risk factors. We retrospectively evaluated comprehensive thrombophilia data from 42 preselected RVO patients without cardiovascular risk factors. The prevalences of different gene mutations and polymorphisms including factor V Leiden mutation G1691A (FVL), FV A4070G, prothrombin mutation G20210A, PT A19911G, and PAI-1 4G/5G were compared with 241 healthy controls matched for age and sex. A total of 20 patients (47.7%) were found to carry thrombophilic gene polymorphisms including FVL, FV A4070G, and homozygous PT A19911G compared with 72 of 241 controls (29.9%; p = 0.03). Subgroup analysis of patients with a significant personal or family history of thromboembolism revealed a high prevalence of FVL, FV A4070G, and homozygous PT A19911G (p = 0.005). FV A4070G was found to be significantly associated with at least two other heterozygous or one homozygous gene polymorphisms (p = 0.02). Multivariate analysis revealed the presence of FVL (p = 0.0017) and homozygous PT A19911G (p = 0.03) polymorphism as independent risk factors for the development of RVO. Our results indicate that in selected RVO patients screening for thrombophilic gene polymorphisms including FVL, FV A4070G and homozygous PT G19911A may be helpful in a high percentage of cases. Our findings suggest that hereditary thrombophilia associated with RVO is more likely to be multigenic than caused by any single risk factor.

Association of transforming growth factor-beta1 gene polymorphism in the development of Epstein-Barr virus-related hematologic diseases.

PubMed

Hatta, Kanako; Morimoto, Akira; Ishii, Eiichi; Kimura, Hiroshi; Ueda, Ikuyo; Hibi, Shigeyoshi; Todo, Shinjiro; Sugimoto, Tohru; Imashuku, Shinsaku

2007-11-01

Epstein-Barr virus (EBV) is etiologically associated with various hematologic disorders, including primary acute infectious mononucleosis (IM), hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV infection (CAEBV) and malignant lymphomas. Although cytokines play a central role in EBV-related immune responses, the exact mechanisms causing different clinical responses remain unclear. In this study, the pattern of cytokine gene polymorphisms was comparatively analyzed in EBV-related diseases. Eighty-nine patients with EBV-related disease were analyzed; 30 with IM, 28 with EBV-HLH and 31 with CAEBV. Eighty-one EBV-seropositive healthy adults were also used as controls. Associations with polymorphisms of various cytokines, including interleukin (IL)-1 alpha and IL-1 beta were evaluated. The gene polymorphisms were typed by polymerase chain reaction with sequence-specific primers. A significant difference of polymorphisms was found for transforming growth factor (TGF)-beta1; the frequency of TGF-beta1 codon 10 C allele was significantly higher in patients with EBV-related diseases than in controls (p<0.001). The difference was significant in patients with IM or HLH (p<0.001), but not in those with CAEBV (p=0.127), compared with controls. As regards other cytokines, the frequency of the IL-1 alpha -889 C allele was significantly lower in patients with IM than in controls (p<0.05). Our results suggests that TGF-beta1 codon 10 C allele plays a role in the development of EBV-related diseases and that the IL-1 alpha -889 C allele may be involved in response failure and sequential progression into the development of HLH.

The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder.

PubMed

Koh, Kyung Bong; Choi, Eun Hee; Lee, Young-joon; Han, Mooyoung; Choi, Sang-Sup; Kim, So Won; Lee, Min Goo

2012-02-01

It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. © Copyright 2012 Physicians Postgraduate Press, Inc.

Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

PubMed Central

Wang, Chun; Gong, Jianping; Wu, Hao

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease. PMID:28804621

High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density.

PubMed

Giroux, Sylvie; Elfassihi, Latifa; Clément, Valérie; Bussières, Johanne; Bureau, Alexandre; Cole, David E C; Rousseau, François

2010-11-01

Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women. Copyright © 2010 Elsevier Inc. All rights reserved.

Promoter polymorphisms in genes involved in porcine myogenesis influence their transcriptional activity.

PubMed

Bongiorni, Silvia; Tilesi, Francesca; Bicorgna, Silvia; Iacoponi, Francesca; Willems, Daniela; Gargani, Maria; D'Andrea, MariaSilvia; Pilla, Fabio; Valentini, Alessio

2014-11-07

Success of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes. We tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and

The effects of polymorphisms in 7 candidate genes on resistance to Salmonella Enteritidis in native chickens.

PubMed

Tohidi, R; Idris, I B; Malar Panandam, J; Hair Bejo, M

2013-04-01

Salmonella enterica serovar Enteritidis infection is a common concern in poultry production for its negative effects on growth as well as food safety for humans. Identification of molecular markers that are linked to resistance to Salmonella Enteritidis may lead to appropriate solutions to control Salmonella infection in chickens. This study investigated the association of candidate genes with resistance to Salmonella Enteritidis in young chickens. Two native breeds of Malaysian chickens, namely, Village Chickens and Red Junglefowl, were evaluated for bacterial colonization after Salmonella Enteritidis inoculation. Seven candidate genes were selected on the basis of their physiological role in immune response, as determined by prior studies in other genetic lines: natural resistance-associated protein 1 (NRAMP1), transforming growth factor β3 (TGFβ3), transforming growth factor β4 (TGFβ4), inhibitor of apoptosis protein 1 (IAP1), caspase 1 (CASP1), lipopolysaccharide-induced tumor necrosis factor (TNF) α factor (LITAF), and TNF-related apoptosis-inducing ligand (TRAIL). Polymerase chain reaction-RFLP was used to identify polymorphisms in the candidate genes; all genes exhibited polymorphisms in at least one breed. The NRAMP1-SacI polymorphism correlated with the differences in Salmonella Enteritidis load in the cecum (P = 0.002) and spleen (P = 0.01) of Village Chickens. Polymorphisms in the restriction sites of TGFβ3-BsrI, TGFβ4-MboII, and TRAIL-StyI were associated with Salmonella Enteritidis burden in the cecum, spleen, and liver of Village Chickens and Red Junglefowl (P < 0.05). These results indicate that the NRAMP1, TGFβ3, TGFβ4, and TRAIL genes are potential candidates for use in selection programs for increasing genetic resistance against Salmonella Enteritidis in native Malaysian chickens.

No association of apolipoprotein B gene polymorphism and blood lipids in obese Egyptian subjects.

PubMed

Bogari, Neda M; Abdel-Latif, Azza M; Hassan, Maha A; Ramadan, Abeer; Fawzy, Ahmed

2015-03-18

Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations. Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism. This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.

The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

PubMed Central

Tong, Xiang; Ma, Yao; Niu, Xundong; Yan, Zhipeng; Liu, Sitong; Peng, Bo; Peng, Shifeng; Fan, Hong

2016-01-01

G16071A gene polymorphism was truly associated with sarcoidosis susceptibility (A vs G, FPRP < 0.001). Additionally, the FPRP test confirmed that the BTNL2 G16071A gene polymorphism was associated only with granulomatous disease susceptibility among Caucasians (A vs G, FPRP < 0.001) at the level of a prior probability, which was 0.001. Conclusion: The meta-analysis indicated that BTNL2 G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians. PMID:27472712

WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

PubMed

Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

2016-03-01

Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

PubMed Central

Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

2016-01-01

Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

Ghrelin gene polymorphisms in rheumatoid arthritis.

PubMed

Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

2011-07-01

Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

PubMed

Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

2011-03-01

Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

Apolipoprotein C3 Gene Polymorphisms Are Not a Risk Factor for Developing Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

PubMed Central

Zhang, Haiying; Chen, Lizhen; Xin, Yongning; Lou, Yuangui; Liu, Yang; Xuan, Shiying

2014-01-01

Context: Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations. Evidence Acquisition: We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations. Results: Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177/1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22),which was not statistically significant (P > 0.05). Conclusions: Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world. PMID:25477977

FLT-1 gene polymorphisms and protein expression profile in rheumatoid arthritis

PubMed Central

Paradowska-Gorycka, Agnieszka; Sowinska, Anna; Pawlik, Andrzej; Malinowski, Damian; Stypinska, Barbara; Haladyj, Ewa; Romanowska-Prochnicka, Katarzyna; Olesinska, Marzena

2017-01-01

Objectives Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different “angiogenic diseases” suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA. Methods The FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated. Results The FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D’ = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls. Conclusion FLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA. PMID:28323906

[Association between platelet-activating factor acetylhydrolase gene polymorphisms and gastrointestinal bleeding in children with Henoch-Schönlein purpura].

PubMed

Wang, Bao-Xiang; Mei, Hong; Peng, Han-Ming; Gao, Yuan; Ding, Yan

2017-04-01

To study the association between the single nucleotide polymorphisms (SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase (PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schönlein purpura (HSP). A total 516 children with HSP were enrolled, among whom 182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR was used to investigate the distribution of genotypes and alleles in the SNPs of Val97Phe. The plasma PAF-AH activity was measured, as well as the levels of platelet-activating factor (PAF), granular membrane protein-140 (GMP-140), β-thromboglobulin (β-TG), and platelet factor 4 (PF4). The Val279Phe genotype and allele frequencies were in Hardy-Weinberg equilibrium, and the homozygous genotype TT and heterozygotes accounted for 0.97% and 6.05% respectively. The gastrointestinal bleeding group had a significantly higher allele frequency than the control group (5.22% vs 3.33%; P<0.01). The HSP patients with GG genotype in the gastrointestinal bleeding group had significantly higher levels of plasma PAF and GMP-140 than those in the non-gastrointestinal bleeding group (P<0.05), while the non-gastrointestinal bleeding group had a significantly higher PAF-AH activity than the gastrointestinal bleeding group (P<0.05). There were no significant differences in β-TG and PF4 between the two groups (P>0.05). Val279Phe gene polymorphisms in PAF-AH are associated with PAF-AH activity and PAF and GMP-140 levels and may be a risk factor for HSP with gastrointestinal bleeding.

CTLA-4 and IL-6 gene polymorphisms: Risk factors for recurrent pregnancy loss.

PubMed

Nasiri, Mahboobeh; Rasti, Zarnegar

2016-12-01

The purpose of the present study was to evaluate the possible association between CTLA-4 +49A/G and IL-6 -634C/G polymorphisms, and the risk of recurrent pregnancy loss (RPL). 240 women (120 healthy controls and 120 with RPL) were enrolled in this case-control study. Genotyping was performed using a PCR-RFLP technique. In the case of polymorphic CTLA-4 +49A/G, the wild type allele G was associated with a decreased risk of RPL (OR: 0.42, 95%CI: 0.25-0.69, p=0.001). As to IL-6 -634C/G polymorphism, a highly significant difference was observed, and those women who carry at least one mutant G allele presented a probability of developing RPL about 5 times greater than controls (OR: 5.1, 95%CI: 1.04-25.3, p=0.04). The results indicate that polymorphisms of CTLA-4 and IL-6 genes may influence the risk of developing RPL among Iranian women, suggesting that more research on the immunogenetics of pregnancy should be conducted to confirm our results, and to declare the exact roles of studied molecules in RPL pathogenesis. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.

PubMed

Shatwan, Israa M; Winther, Kristian Hillert; Ellahi, Basma; Elwood, Peter; Ben-Shlomo, Yoav; Givens, Ian; Rayman, Margaret P; Lovegrove, Julie A; Vimaleswaran, Karani S

2018-04-30

Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10 - 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10 - 4 ) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10 - 6 and P = 3 × 10 - 4 , respectively) was further replicated in the CaPS. Additionally, significant

The CIDEA gene V115F polymorphism is associated with obesity in Swedish subjects.

PubMed

Dahlman, Ingrid; Kaaman, Maria; Jiao, Hong; Kere, Juha; Laakso, Markku; Arner, Peter

2005-10-01

The cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) gene is implicated as an important regulator of body weight in mice and humans and is therefore a candidate gene for human obesity. Here, we characterize common CIDEA gene polymorphisms and investigate them for association with obesity in two independent Swedish samples; the first comprised 981 women and the second 582 men. Both samples display a large variation in BMI. The only detected coding polymorphism encodes an exon 4 V115F amino acid substitution, which is associated with BMI in both sexes (P = 0.021 for women, P = 0.023 for men, and P = 0.0015 for joint analysis). These results support a role for CIDEA alleles in human obesity. CIDEA-deficient mice display higher metabolic rate, and the gene cross-talks with tumor necrosis factor-alpha (TNF-alpha) in fat cells. We hypothesize that CIDEA alleles regulate human obesity through impact on basal metabolic rate and adipocyte TNF-alpha signaling.

Association between rs2981582 polymorphism in the FGFR2 gene and the risk of breast cancer in Mexican women

PubMed Central

Murillo-Zamora, Efrén; Moreno-Macías, Hortensia; Ziv, Elad; Romieu, Isabelle; Lazcano-Ponce, Eduardo; Ángeles-Llerenas, Angélica; Pérez-Rodríguez, Edelmiro; Vidal-Millán, Silvia; Fejerman, Laura; Torres-Mejía, Gabriela

2014-01-01

Background and Aims The rs2981582 single nucleotide polymorphism in the Fibroblast Growth Factor Receptor 2 gene has been consistently associated with an increased risk of breast cancer. We evaluated the effect of rs2981582 polymorphism in the FGFR2 gene on the risk of breast cancer and its interaction with non-genetic risk factors. Methods A population based case control study was conducted in Mexico. Data from 687 cases and 907 controls were analyzed. Results The T allele of the rs2981582 polymorphism was associated with an increased risk of breast cancer (OR per allele =1.24, 95% CI 1.06 – 1.46). There was also an interaction between this polymorphism and alcohol consumption (p = 0.043); the effect of alcohol consumption on the risk of breast cancer varied according to the allelic variants of the rs2981582 polymorphism in the FGFR2 gene: OR = 3.97 (95% CI 2.10 – 7.49), OR = 2.01 (95% CI 1.23 − 3.29) and OR = 1.21 (95% CI 0.48 − 3.05) for genotypes CC, CT and TT, respectively. Conclusions This is the first study exploring the association between rs2981582 polymorphism in the FGFR2 gene and breast cancer risk in Mexican women. The interaction found may be of great public health interest, since alcohol consumption is a modifiable breast cancer risk factor. Therefore, replication of this finding is of foremost importance. PMID:24054997

Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

PubMed

Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

2015-09-29

Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

[Association of Val66Met polymorphism of brain-derived neurotrophic factor gene with cognitive impairment and clinical symptoms in first episode schizophrenia].

PubMed

Zhang, Chengcheng; Gu, Xiaochu; Wang, Qiang; Li, Mingli; Deng, Wei; Guo, Wanjun; Zhao, Liansheng; Ma, Xiaohong; Li, Tao

2017-08-10

To assess the association of cognitive impairment and clinical symptoms in first-episode schizophrenia with the Val66Met (rs6265) polymorphism of brain-derived neurotrophic factor (BDNF) gene. For 87 patients with first-episode schizophrenia and 76 healthy controls, the Val66Met polymorphism was determined with a Taqman Assay-on-Demand method. Wechsler intelligence test was carried out for all participants. Correlation of cognitive impairment with clinical severity was also analyzed. The patients were significantly lower in total IQ, verbal IQ and performance IQ compared to the controls. The lower total IQ (F=4.59, P= 0.01) and verbal IQ (F=4.44, P=0.01) were influenced by genetic factors and diagnostic interaction. The vertal IQ of Val/Val patients was significantly lower than those of Val/Met and Met/Met carriers. For the control group, the verbal IQ of Met/Met carriers was lower than that of Val/Met carriers, and the total IQ of Met/Met carriers was lower than those of Val/Met and Val/Val carriers. For the patient group, the total IQ of Val/Val carriers was negatively correlated with positive symptoms (r=-0.65, P=0.03) and thought disorders (r=-0.61, P=0.02). Cognitive impairment in first-episode schizophrenic patients is associated with the Val66Met polymorphism of the BDNF gene, and has an important clinical relevance.

A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS.

PubMed

Cheeran, Binith; Talelli, Penelope; Mori, Francesco; Koch, Giacomo; Suppa, Antonio; Edwards, Mark; Houlden, Henry; Bhatia, Kailash; Greenwood, Richard; Rothwell, John C

2008-12-01

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.

Transforming Growth Factor-β1 Gene Polymorphism (T29C) in Egyptian Patients with Hepatitis B Virus Infection: A Preliminary Study

PubMed Central

Talaat, Roba M.; Dondeti, Mahmoud F.; El-Shenawy, Soha Z.; Khamiss, Omaima A.

2013-01-01

The interindividual variations in the capacity of transforming growth factor-β1 (TGF-β1) production have been ascribed to genetic polymorphisms in TGF-β1 gene. As pathogenesis of HBV has a genetic background, this preliminary study was designed to assess the impact of TGF-β1 (T29C) on the susceptibility of Egyptians to HBV infection. Genotyping was performed using single stranded polymorphism-polymerase chain reaction (SSP-PCR) in 65 Egyptian hepatitis B patients and 50 healthy controls. TGF-β1 plasma levels were measured using Enzyme-linked immunosorbent assay (ELISA). The frequency of CC genotype was significantly higher (P < 0.05) in HBV patients compared to controls. On the contrary, TC genotype did not show significant difference in both groups. TT genotype was significantly higher (P < 0.01) in controls than HBV patients. Our current preliminary data revealed that the frequency of the genotypes in the controls were within Hardy-Weinberg equilibrium (HWE) while the patients group was out of HWE (P < 0.01). TGF-β1 was significantly (r = −0.684; P < 0.001) deceased in the sera of patients as compared to normal subjects. Depending on our preliminary work, CC genotype may act as a host genetic factor in the susceptibility to HBV infection in Egyptians. Taken together, the current data pointed to the importance of polymorphism of TGF-β1 gene (T29C) in HBV infection. PMID:24455227

Impact of Blood Type, Functional Polymorphism (T-1676C) of the COX-1 Gene Promoter and Clinical Factors on the Development of Peptic Ulcer during Cardiovascular Prophylaxis with Low-Dose Aspirin

PubMed Central

Wang, Pin-Yao; Chen, Hsiu-Ping; Chen, Angela; Tsay, Feng-Woei; Kao, Sung-Shuo; Peng, Nan-Jing; Tseng, Hui-Hwa; Hsu, Ping-I

2014-01-01

Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin. PMID:25243161

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized

[The value of 5-HTT gene polymorphism for the assessment and prediction of male adolescence violence].

PubMed

Yu, Yue; Liu, Xiang; Yang, Zhen-xing; Qiu, Chang-jian; Ma, Xiao-hong

2012-08-01

To establish an adolescent violence crime prediction model, and to assess the value of serotonin transporter (5-HTT) gene polymorphism for the assessment and prediction of violent crime. Investigative tools were used to analyze the difference in personality dimensions, social support, coping styles, aggressiveness, impulsivity, and family condition scale between 223 adolescents with violence behavior and 148 adolescents without violence behavior. The distribution of 5-HTT gene polymorphisms (5-HTTLPR and 5-HTTVNTR) was compared between the two groups. The role of 5-HTT gene polymorphism on adolescent personality, impulsion and aggression scale also was also analyzed. Stepwise logistic regression was used to establish a predictive model for adolescent violent crime. Significant difference was found between the violence group and the control group on multiple dimensions of psychology and environment scales. However, no statistical difference was found with regard to the 5-HTT genotypes and alleles between adolescents with violent behaviors and normal controls. The rate of prediction accuracy was not significantly improved when 5-HTT gene polymorphism was taken into the model. The violent crime of adolescents was closely related with social and environmental factors. No association was found between 5-HTT polymorphisms and adolescent violence criminal behavior.

Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer

PubMed Central

Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

2014-01-01

Purpose The mismatch repair (MMR) system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in the MMR proteins have a 102 –103-fold increase in the mutation rate. Single nucleotide polymorphisms (SNPs) of MMR genes have been shown to cause a reduction in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer (PC) and that p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. Material and Methods DNA samples from 110 cases of prostate cancer and healthy controls (n=110) were analyzed by SSCP and PCR-RFLP to determine the genotypic frequency of five different polymorphic loci on two MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare the genotype frequency between patients and controls. Results A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR, 1.87; 95% CI, 1.0–3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR, 1.57; 95% CI, 0.92–2.72). Among p53 codon72 Arg/Pro + Pro/Pro carriers, the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR = 2.1, 95% CI; 1.05–4.34). Conclusion This is the first report on the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer. PMID:18355840

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

PubMed Central

Ferguson, Lynnette R; Huebner, Claudia; Petermann, Ivonne; Gearry, Richard B; Barclay, Murray L; Demmers, Pieter; McCulloch, Alan; Han, Dug Yeo

2008-01-01

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn’s disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes. PMID:18698679

Uncoupling protein 2 gene polymorphisms are associated with obesity

PubMed Central

2012-01-01

Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

Polymorphisms in aryl hydrocarbon receptor gene are associated with idiopathic male factor infertility.

PubMed

Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Saba

2013-12-01

We wanted to determine whether genetic polymorphisms of aryl hydrocarbon receptor (AhR) gene are associated with susceptibility to male infertility. This study comprised 176 men with idiopathic infertility and 352 healthy fertile men who served as controls. Seven single-nucleotide polymorphisms (SNPs) of the AhR gene (rs2066853, rs1476080, rs10250822, rs10247158, rs2282885, rs6960165, and rs7811989) were selected and genotyped by the polymerase chain reaction-restriction fragment length polymorphism analysis. The serum levels of reproductive and thyroid hormones and inhibin B were also measured. After multiple regression analysis, 2 of the 7 studied SNPs were significantly associated with the occurrence of male infertility. Men with rs2066853 AA genotype had 33% decreased risk of being infertile (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.46-0.87; P = .003). The C allele of rs2282885 was significantly associated with infertility risk, with an OR of 2.14 (95% CI: 1.64-3.72) for heterozygotes and 3.54 (95% CI: 2.25-5.84) for homozygotes. When haplotypes were composed of 7 AhR SNP sites, patients with AACACAG haplotype harbored more than 75% decreased risk of being infertile (OR = 0.21, 95% CI: 0.11-0.32; P = .001). Conversely, carriers of the AACACGA haplotype had more than 12-fold increased risk of being infertile (OR = 12.62, 95% CI: 2.77-52.74; P = .00001). Homozygosity for the rs2066853 A allele and rs2282885 C allele decreases and increases the risk of developing male infertility, respectively.

Screening strategies for a highly polymorphic gene: DHPLC analysis of the Fanconi anemia group A gene.

PubMed

Rischewski, J; Schneppenheim, R

2001-01-30

Patients with Fanconi anemia (Fanc) are at risk of developing leukemia. Mutations of the group A gene (FancA) are most common. A multitude of polymorphisms and mutations within the 43 exons of the gene are described. To examine the role of heterozygosity as a risk factor for malignancies, a partially automatized screening method to identify aberrations was needed. We report on our experience with DHPLC (WAVE (Transgenomic)). PCR amplification of all 43 exons from one individual was performed on one microtiter plate on a gradient thermocycler. DHPLC analysis conditions were established via melting curves, prediction software, and test runs with aberrant samples. PCR products were analyzed twice: native, and after adding a WT-PCR product. Retention patterns were compared with previously identified polymorphic PCR products or mutants. We have defined the mutation screening conditions for all 43 exons of FancA using DHPLC. So far, 40 different sequence variations have been detected in more than 100 individuals. The native analysis identifies heterozygous individuals, and the second run detects homozygous aberrations. Retention patterns are specific for the underlying sequence aberration, thus reducing sequencing demand and costs. DHPLC is a valuable tool for reproducible recognition of known sequence aberrations and screening for unknown mutations in the highly polymorphic FancA gene.

Polymorphisms within the tumor necrosis factor and lymphotoxin-alpha genes and endemic pemphigus foliaceus--are there any associations?

PubMed

Roxo, V M M S; Pereira, N F; Pavoni, D P; Lin, M-T; Hansen, J A; de O Poersch, C; Filho, A Marquart; Petzl-Erler, M L

2003-11-01

The purpose of this study was to analyze the possible influence of the TNF and LTA loci polymorphisms on the susceptibility/resistance to endemic pemphigus foliaceus, also named fogo selvagem (FS), an autoimmune disease characterized by blisters due to acantholysis of the superficial-most epidermal cells. Autoantibodies, mainly of the IgG4 subclass, are directed against a desmosomal glycoprotein known as desmoglein 1. FS shares clinical, histological and immunological features with nonendemic pemphigus foliaceus. Most residents of the endemic regions do not develop the disease, and familial clustering has been documented, suggesting that host factors play a role in susceptibility. In fact, strong positive and negative associations with HLA class II genes have been reported. The TNF and LTA genes are located in the class III region of the Human Major Histocompatibility Complex. Their location, the function of their products, which are cytokines and pluripotent immunomodulators, as well as their genetic variability make them candidate genes for complex diseases with an altered immune response. A total of 162 patients and 191 controls were enrolled in this study. No significant associations were found with any one of the three LTA single nucleotide polymorphisms (SNP) analyzed (at nucleotides 249, 365, 720), nor with the TNF SNP located at positions -863 and -308. The frequency of allele TNF*238A was slightly decreased in patients (OR = 0.45). In conclusion, the results of this study indicate that genetic variability of the TNF and LTA genes does not play a major role in susceptibility/resistance to pemphigus foliaceus.

Association of interleukin 18, interleukin 2, and tumor necrosis factor polymorphisms with subacute sclerosing panencephalitis.

PubMed

Piskin, Ibrahim Etem; Karakas-Celik, Sevim; Calik, Mustafa; Abuhandan, Mahmut; Kolsal, Ebru; Genc, Gunes Cakmak; Iscan, Akin

2013-06-01

Subacute sclerosing panencephalitis (SSPE) is a progressive inflammatory and degenerative disorder of the central nervous system. The measles virus (MV) and host and environmental factors are involved in the development of SSPE, but the precise mechanism by which the MV causes SSPE is still unknown. Studies have indicated that in SSPE patients, specific polymorphisms of certain genes are most likely involved in impairing the host's ability to eradicate the MV. The purpose of our study was to elucidate the role of polymorphisms in the genes encoding interleukin (IL)-2, IL-18, and tumor necrosis factor alpha (TNF-α) in the development of SSPE. Using the polymerase chain reaction with sequence-specific primers, the single-nucleotide polymorphisms (SNPs) of the promoter regions of IL-2 (-330), TNF-α (-308), and IL-18 (-137 and -607) were studied in 54 patients with SSPE and 72 healthy controls. The frequency of SSPE patients with the AA genotype of IL-18 at position -607 was significantly higher than the frequency of those with the CC genotype (p<0.001, odds ratio [OR]: 5.76), and a significantly higher proportion of patients had the C allele at -137 compared with the controls (p=0.002, OR: 2.72). In a haplotype analysis of two SNPs in the IL-18 gene, the frequency of the CA haplotype was significantly higher in SSPE patients (p<0.001, OR: 3.99) than in the controls. The IL-2 (-330) and TNF-α (-308) polymorphisms revealed no significant differences. In conclusion, these data suggest that the IL-18 gene polymorphisms at position -607 and -137 might be genetic risk factors for the SSPE disease.

Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer’s disease: a pilot study

PubMed Central

Toral-Rios, Danira; Franco-Bocanegra, Diana; Rosas-Carrasco, Oscar; Mena-Barranco, Francisco; Carvajal-García, Rosa; Meraz-Ríos, Marco Antonio; Campos-Peña, Victoria

2015-01-01

Amyloid peptide is able to promote the activation of microglia and astrocytes in Alzheimer’s disease (AD), and this stimulates the production of pro-inflammatory cytokines. Inflammation contributes to the process of neurodegeneration and therefore is a key factor in the development of AD. Some of the most important proteins involved in AD inflammation are: clusterin (CLU), complement receptor 1 (CR1), C reactive protein (CRP), tumor necrosis factor α (TNF-α), the interleukins 1α (IL-1α), 6 (IL-6), 10 (IL-10) and cyclooxygenase 2 (COX-2). In particular, COX-2 is encoded by the prostaglandin-endoperoxide synthase 2 gene (PTGS2). Since variations in the genes that encode these proteins may modify gene expression or function, it is important to investigate whether these variations may change the developing AD. The aim of this study was to determine whether the presence of polymorphisms in the genes encoding the aforementioned proteins is associated in Mexican patients with AD. Fourteen polymorphisms were genotyped in 96 subjects with AD and 100 controls; the differences in allele, genotype and haplotype frequencies were analyzed. Additionally, an ancestry analysis was conducted to exclude differences in genetic ancestry among groups as a confounding factor in the study. Significant differences in frequencies between AD and controls were found for the single-nucleotide polymorphism (SNP) rs20417 within the PTGS2 gene. Ancestry analysis revealed no significant differences in the ancestry of the compared groups, and the association was significant even after adjustment for ancestry and correction for multiple testing, which strengthens the validity of the results. We conclude that this polymorphism plays an important role in the development of the AD pathology and further studies are required, including their proteins. PMID:26041990

The importance of association between angiotensin-converting enzyme (ACE) Gene I/D polymorphism and diabetic peripheral neuropathy.

PubMed

Inanir, Ahmet; Basol, Nursah; Karakus, Nevin; Yigit, Serbulent

2013-11-10

Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus (DM) due to decreasing quality of life. In the present study, it is aimed to evaluate angiotensin-converting enzyme (ACE) Gene I/D polymorphism in Turkish population. Two hundred and thirty-five DPN patients and two hundred and eighty-one controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the ACE gene I/D polymorphism. Baseline characteristics of the DPN patients according to ACE genotypes were similar, except for history of hypertension. The frequency of II genotype was significantly higher in patients with positive history of hypertension than the patients with negative history of hypertension (p=0.013). DD genotype of I/D polymorphism was found to be a susceptibility factor for DPN in homozygous form (p=0.032). According to allele frequencies, D allele of I/D polymorphism was found to be a susceptibility factor for DPN (p=0.031). ACE gene I/D polymorphism may research in DM patients to determine genetic predisposition for DPN. It can be useful for taking early measures and avoiding DPN in a Turkish population. © 2013 Elsevier B.V. All rights reserved.

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis.

PubMed

Lankarani, Kamran B; Karbasi, Ashraf; Kalantari, Tahereh; Yarmohammadi, Hooman; Saberi-Firoozi, Mehdi; Alizadeh-Naeeni, Mahvash; Taghavi, Ali R; Fattahi, Mahammad R; Ghaderi, Abbas

2006-02-01

Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CTLA-4 polymorphism is not associated with UC in the Iranian population.

Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

PubMed

El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef

2014-11-01

Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

Identification and characterization of single nucleotide polymorphisms in 6 growth-correlated genes in porcine by denaturing high performance liquid chromatography.

PubMed

Liu, Dewu; Zhang, Yushan; Du, Yinjun; Yang, Guanfu; Zhang, Xiquan

2007-06-01

The growth-correlated genes that are part of the neuroendocrine growth axis play crucial roles in the regulation of growth and development of pig. The identification of genetic polymorphisms in these genes will enable the scientist to evaluate the biological relevance of such polymorphisms and to gain a better understanding of quantitative traits like growth. In the present study, seven pairs of primers were designed to obtain unknown sequences of growth-correlated genes, and other 25 pairs of primers were designed to identify single nucleotide polymorphisms (SNP) using the denaturing high-performance liquid chromatography (DHPLC) technology in four pig breeds (Duroc, Landrace, Lantang and Wuzhishan), significantly differing in growth and development characteristics. A total of 101 polymorphisms were discovered in 10,707 base pairs (bp) from six genes of the ghrelin (GHRL), leptin (LEP), insulin-like growth factor II (IGF-II), insulin-like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor binding protein 3 (IGFBP-3), and somatostatin (SS). The observed average distances between the SNP in the 5'UTR, coding regions, introns and 3'UTR were 134, 521, 81 and 92 bp, respectively. Four SNPs were found in the coding regions of IGF-II, IGFBP-2 and LEP, respectively. Two synonymous mutations were obtained in IGF-II and LEP genes respectively, and two non-synonymous were found in IGFBP-2 and LEP genes, respectively. Seven other mutations were also observed. Thirty-two PCR-RFLP markers were found among 101 polymorphisms of the six genes. The SNP discovered in this study would provide suitable markers for association studies of candidate genes with growth related traits in pig.

Tumor necrosis factor alpha (-308), interleukin-6 (-174) and interleukin-10 (-1082) gene polymorphisms in polycystic ovary syndrome.

PubMed

Vural, Pervin; Değirmencioğlu, Sevgin; Saral, Neslihan Y; Akgül, Cemil

2010-05-01

The imbalance between pro- and anti-inflammatory cytokines and polymorphism of cytokine genes may play a role in the etiology of the polycystic ovary syndrome (PCOS). The aim of this study was to investigate the association of polymorphisms of TNFalpha, IL-6 and IL-10 genes with the occurrence and the clinical/laboratory characteristics of PCOS in the Turkish population. Single nucleotide polymorphisms (SNPs) of TNFalpha (-308 G/A), IL-6 (-174 G/C), IL-10 (-1082 G/A) genes in DNA from peripheral blood leukocytes of 97 PCOS patients and 95 healthy control women were investigated. There is a tendency toward lower frequency of the IL-6 CC genotype and C allele among PCOS women compared with healthy controls although the difference did not reach a significant level. No notable differences were observed in allele or genotype frequencies for TNFalpha and IL-10 genes between groups. The concomitant presence of wild homozygous TNFalpha genotype together with mutant IL-6 C allele has a protective effect against PCOS with an OR=0.45 (95% CI=0.23-0.86). While TNFalpha (-308) and IL-10 (-1082) genotypes did not influence clinical/laboratory parameters in PCOS, IL-6 (-174) CC or pooled CG+CC genotypes have lower glucose, insulin, HOMA, cholesterol, triglyceride, and LDL-C, and higher GIR and HDL-C values than GG genotypes. We suggest that the IL-6 promoter region polymorphism may be related to occurrence and metabolic abnormalities seen in PCOS in the Turkish population. However, more studies with larger sample size are necessary to support our findings in other populations before any statement can be made about the relationship between PCOS and cytokine polymorphism. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

The sheep growth hormone gene polymorphism and its effects on milk traits.

PubMed

Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Paschino, Pietro; Vacca, Giuseppe Massimo

2015-05-01

Growth hormone (GH) is encoded by the GH gene, which may be single copy or duplicate in sheep. The two copies of the sheep GH gene (GH1/GH2-N and GH2-Z) were entirely sequenced in one 106 ewes of Sarda breed, in order to highlight sequence polymorphisms and investigate possible association between genetic variants and milk traits. Milk traits included milk yield, fat, protein, casein and lactose percentage. We evidenced 75 nucleotide changes. Transcription factor binding site prediction revealed two sequences potentially recognised by the pituitary-specific transcription factor POU1FI at the GH1/GH2-N gene, which were lost at the promoter of GH2-Z, which might explain the different tissues of expression of GH1/GH2-N (pituitary) and GH2-Z (placenta). Significant differences in milk traits were observed among genotypes at polymorphic loci only for the GH2-Z gene. Sheep with homozygote genotype ss748770547 CC had higher fat percentage (P < 0.01) than TT. SNP ss748770547 was part of a potential transcription factor binding site for C/EBP alpha (CCAAT/Enhancer Binding Protein), which is involved in the regulation of adipogenesis and adipoblast differentiation. SNP ss748770547, located in the GH2-Z gene 5' flanking region, may be a causal mutation affecting milk fat content. These findings might contribute to the knowledge of the sheep GH locus and might be useful in selection processes in sheep.

Gene polymorphisms as risk factors for predicting the cardiovascular manifestations in Marfan syndrome. Role of folic acid metabolism enzyme gene polymorphisms in Marfan syndrome.

PubMed

Benke, Kálmán; Ágg, Bence; Mátyás, Gábor; Szokolai, Viola; Harsányi, Gergely; Szilveszter, Bálint; Odler, Balázs; Pólos, Miklós; Maurovich-Horvat, Pál; Radovits, Tamás; Merkely, Béla; Nagy, Zsolt B; Szabolcs, Zoltán

2015-10-01

Folic acid metabolism enzyme polymorphisms are believed to be responsible for the elevation of homocysteine (HCY) concentration in the blood plasma, correlating with the pathogenesis of aortic aneurysms and aortic dissection. We studied 71 Marfan patients divided into groups based on the severity of cardiovascular involvement: no intervention required (n=27, Group A); mild involvement requiring intervention (n=17, Group B); severe involvement (n=27, Group C) subdivided into aortic dilatation (n=14, Group C1) and aortic dissection (n=13, Group C2), as well as 117 control subjects. We evaluated HCY, folate, vitamin B12 and the polymorphisms of methylenetetrahydrofolate reductase (MTHFR;c.665C>T and c.1286A>C), methionine synthase (MTR;c.2756A>G) and methionine synthase reductase (MTRR;c.66A>G). Multiple comparisons showed significantly higher levels of HCY in Group C2 compared to Groups A, B, C1 and control group (p<0.0001, p<0.0001, p=0.001 and p=0.003, respectively). Folate was lower in Group C2 than in Groups A, B, C1 and control subjects (p<0.0001, p=0.02, p<0.0001 and p<0.0001, respectively). Group C2 had the highest prevalence of homozygotes for all four gene polymorphisms. Multivariate logistic regression analysis revealed that HCY plasma level was an independent risk factor for severe cardiovascular involvement (Group C; odds ratio [OR] 1.85, 95% confidence interval [CI] 1.28-2.67, p=0.001) as well as for aortic dissection (Group C2; OR 2.49, 95%CI 1.30-4.78, p=0.006). In conclusion, severe cardiovascular involvement in Marfan patients, and especially aortic dissection, is associated with higher HCY plasma levels and prevalence of homozygous genotypes of folic acid metabolism enzymes than mild or no cardiovascular involvement. These results suggest that impaired folic acid metabolism has an important role in the development and remodelling of the extracellular matrix of the aorta.

Wheat CBF gene family: identification of polymorphisms in the CBF coding sequence.

PubMed

Mohseni, Sara; Che, Hua; Djillali, Zakia; Dumont, Estelle; Nankeu, Joseph; Danyluk, Jean

2012-12-01

Expression of cold-regulated genes needed for protection against freezing stress is mediated, in part, by the CBF transcription factor family. Previous studies with temperate cereals suggested that the CBF gene family in wheat was large, and that CBF genes were at the base of an important low temperature tolerance trait. Therefore, the goal of our study was to identify the CBF repertoire in the freezing-tolerant hexaploid wheat cultivar Norstar, and then to examine if the coding region of CBF genes in two spring cultivars contain polymorphisms that could affect the protein sequence and structure. Our analyses reveal that hexaploid wheat contains a complex CBF family consisting of at least 65 CBF genes of which 60 are known to be expressed in the cultivar Norstar. They represent 27 paralogous genes with 1-3 homeologous copies for the A, B, and D genomes. The cultivar Norstar contains two pseudogenes and at least 24 additional proteins having sequences and (or) structures that deviate from the consensus in the conserved AP2 DNA-binding and (or) C-terminal activation-domains. This suggests that in cultivars such as Norstar, low temperature tolerance may be increased through breeding of additional optimal alleles. The examination of the CBF repertoire present in the two spring cultivars, Chinese Spring and Manitou, reveals that they have additional polymorphisms affecting conserved positions in these domains. Understanding the effects of these polymorphisms will provide additional information for the selection of optimum CBF alleles in Triticeae breeding programs.

The role of xenobotic metabolism MGST1 gene polymorphism in colorectal cancer patients.

PubMed

Akil, Fardah; Akil, H A M; Lutfie, A M; Wibowo, Wahyu S; Miskad, Upik; Yusuf, Irawan

2012-10-01

to asses the role of Microsomal Glutathione S-Transferase1 (MGST1) gene as one of enzym metabolism that plays in enviromental factor. using case-control study, subjects with age less than 50 years were collected from teaching hospital Makassar between 2008-2010. Frozen or routinely processed tumour samples biopsy and peripheral blood were obtained from 35 CRC patients undergoing surgery and endoscopic examination with 61 subject as control. CRC cases were diagnosis by clinical examination and confirm by histopathology without familial aggregation of CRC. DNA resequencing was conducted for the 3 kb genomic DNA region MGST1 using PCR-restriction fragment length polymorphism (PCR-RFLP). from 96 subject, two varian single nucleotide polymorphisms (SNPs) 16454T>G and 16416G>A MGST1 were identified. Significant CRC association (p= 0.047) was detected in GG genotipe SNP 16454T>G MGST1 with 3.5 fold risk (95% confidence interval (CI) 0.962-13.191). the results suggest that MGST1 gene polymorphisms as one of environment gene may contribute to CRC risk in younger age (<50 years old).

Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

DTIC Science & Technology

2006-06-01

polymorphisms . The specific aims are 1) methodological training in the analysis of gene - gene and gene -environment interactions by studying folate...evaluation of folate intake, plasma folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples...isolated for the folate and gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time and over

Polymorphism at codon 36 of the p53 gene.

PubMed

Felix, C A; Brown, D L; Mitsudomi, T; Ikagaki, N; Wong, A; Wasserman, R; Womer, R B; Biegel, J A

1994-01-01

A polymorphism at codon 36 in exon 4 of the p53 gene was identified by single strand conformation polymorphism (SSCP) analysis and direct sequencing of genomic DNA PCR products. The polymorphic allele, present in the heterozygous state in genomic DNAs of four of 100 individuals (4%), changes the codon 36 CCG to CCA, eliminates a FinI restriction site and creates a BccI site. Including this polymorphism there are four known polymorphisms in the p53 coding sequence.

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

PubMed Central

Imboden, M; Nieters, A; Bircher, AJ; Brutsche, M; Becker, N; Wjst, M; Ackermann-Liebrich, U; Berger, W; Probst-Hensch, NM

2006-01-01

Background Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. Methods Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. Results We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. Conclusion Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes. PMID:16759385

Tumor necrosis factor alpha gene promoter -238G/A polymorphism increases the risk of psoriasis vulgaris in Indian patients.

PubMed

Rajesh, Deepa; Gurumurthy, Rajesh; Kutty, A V Moideen; Balakrishna, Sharath

2017-03-01

Tumor necrosis factor alpha (TNFα) gene -238G/A polymorphism (rs361525) is associated with psoriasis in several populations worldwide. To the best of our knowledge, there is no information about this polymorphism in Indian psoriatic patients. This study was undertaken to fill the gap in knowledge. This case-control study involved 72 patients with psoriasis vulgaris (PsV) and 72 age and gender matched healthy individuals. TNFα -238G/A polymorphism was genotyped by PCR-RFLP method. TNFα -238A allele was 5 times commoner in PsV patients than in the control group (P = 4.1 × 10 -7 ; odds ratio [OR] = 6.5 [0.95 CI: 2.9-14.6]). Distribution of the genotypes in the two groups showed statistically significant difference in dominant genetic model (P = 2.3 × 10 -7 ) and not in recessive genetic model (P = 2.5 × 10 -1 ). Odds ratio for the occurrence of -238A genotype in PsV patients was 8.8 (0.95 CI: 3.5-20.2). The association showed no major difference when PsV patients were subgrouped into type I and type II categories and tested separately. Subgroup analysis on the basis of disease severity showed higher association with the moderate-severe subgroup (P = 2.4 × 10 -9 , OR 15.4 [0.95 CI: 5.8-41.0]) than with mild subgroup (P = 1.3 × 10 -2 , OR 3.8 [0.95 CI: 1.3-10.9]). Our results indicate that TNFα gene -238G/A polymorphism increases the risk of developing psoriasis vulgaris among Indians. Also, the data show that severity and not the type affects the strength of association in this population. © 2017 The International Society of Dermatology.

Polymorphisms in VDR gene in Tunisian postmenopausal women are associated with osteopenia phenotype.

PubMed

Sassi, R; Sahli, H; Souissi, C; Sellami, S; Ben Ammar El Gaaied, A

2015-01-01

Osteopenia is characterized by intermediate values of bone mineral density (BMD) as compared to normal and osteoporotic subjects. BMD, a surrogate phenotype for osteoporosis, is influenced in part by genetic factors. Among the genes associated with BMD, the vitamin D receptor (VDR) was the first gene studied as a potential candidate associated with BMD in adult and postmenopausal bone loss. However, results are controversial. To determine whether VDR polymorphisms ApaI and TaqI are associated with BMD, osteopenia, osteoporosis and low-impact fracture risk in North Africans, these genotypes were analyzed in 566 postmenopausal Tunisian women. In postmenopausal Tunisian women, the GT ApaI genotype seems to be protective against osteoporosis development (p = 0.02; odds ratio = 0.54). Moreover, the presence of the combined GT/TT genotype of ApaI and TaqI polymorphisms is more frequent in normal BMD women than in osteoporotic women (p = 0.00; odds ratio = 0.41). Interestingly, the GG ApaI genotype is associated with osteopenia development (p = 0.02; odds ratio = 1.86) and also the TT TaqI polymorphism (p = 0.02; odds ratio = 1.53). The GG ApaI genotype is associated with a three times risk of vertebral fracture. The ApaI polymorphism showed an association with osteopenia and low-impact vertebral fracture incidence but not with osteoporosis. The TaqI polymorphism is associated specifically with the osteopenia phenotype. The presence of the two polymorphisms increases the risk to develop osteopenia in postmenopausal Tunisian women. Osteopenia seems to be genetically determined. However, osteoporosis is the result of interaction between genetic and environmental factors.

Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age.

PubMed

Shi, Zumin; Johnstone, Daniel; Talseth-Palmer, Bente A; Evans, Tiffany-Jane; Spigelman, Allan D; Groombridge, Claire; Milward, Elizabeth A; Olynyk, John K; Suchy, Janina; Kurzawski, Grzegorz; Lubinski, Jan; Scott, Rodney J

2009-07-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by germline mutations in DNA mismatch repair genes; however, variation in disease expression suggests that there are potential modifying factors. Polymorphisms of the HFE gene, which cause the iron overload disorder hereditary haemochromatosis, have been proposed as potential risk factors for the development of colorectal cancer (CRC). To understand the relationship between HNPCC disease phenotype and polymorphisms of the HFE gene, a total of 362 individuals from Australia and Poland with confirmed causative MMR gene mutations were genotyped for the HFE C282Y and H63D polymorphisms. A significantly increased risk of developing CRC was observed for H63D homozygotes when compared with combined wild-type homozygotes and heterozygotes (hazard ratio = 2.93, p = 0.007). Evidence for earlier CRC onset was also observed in H63D homozygotes with a median age of onset 6 years earlier than wild type or heterozygous participants (44 vs. 50 years of age). This effect was significant by all tests used (log-rank test p = 0.026, Wilcoxon p = 0.044, Tarone-Ware p = 0.035). No association was identified for heterozygosity of either polymorphism and limitations on power-prevented investigation of C282Y homozygosity or compound C282Y/H63D heterozygosity. In the Australian sample only, women had a significantly reduced risk of developing CRC when compared with men (hazard ratio = 0.58, p = 0.012) independent of HFE genotype for either single nucleotide polymorphisms. In conclusion, homozygosity for the HFE H63D polymorphism seems to be a genetic modifier of disease expression in HNPCC. Understanding the mechanisms by which HFE interrelates with colorectal malignancies could lead to reduction of disease risk in HNPCC.

[Association of estrogen receptor gene polymorphism with cerebral infarction, a case-control study].

PubMed

Zhang, Yan; Xie, Ruping; Wang, Yinhua; Chen, Dafang; Wang, Guoying; Xu, Xiping

2002-11-10

To explore the association between estrogen receptor (ER) gene PvuII and XbaI polymorphisms and cerebral infarction among Chinese Han people. Samples of peripheral blood white cell were extracted among 234 patients with cerebral infarction, aged 63.9 +/- 10.3, and 259 controls without cerebrovascular disease, aged 59.2 +/- 9.2, all of Chinese Han nationality. PCR-RFLP and genotyping of ER PvuII and XbaI polymorphisms were performed. Multiple Logistic regression analysis was made to explore the risk factors for cerebral infarction. After adjustment for major confounders including age, gender, smoking, alcohol drinking, education, history of hypertension, diabetes mellitus, coronary artery disease and hyperlipoidemia, multiple Logistic regression analysis showed that: (1) The Pp genotype of ER PvuII polymorphism increased the risk of cerebral infarction significantly (OR = 1.97, 95% CI: 1.21 - 3.21); (2) The ER XbaI polymorphism was not in association with cerebral infarction significantly; (3) The PPXx/Ppxx genotypes increased the risk of cerebral infarction significantly (OR = 1.67, 2.52 and 2.18 respectively, P < 0.05) before or after all subjects were stratified by the history of hypertension or hyperlipoidemia; and (4) The positive interaction between the ER PvuII polymorphism and the presence of hypertension or diabetes or hyperlipoidemia could increase the risk of cerebral infarction significantly. ER gene may be one of the genetic candidate genes for cerebral infarction among Chinese Han population.

Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

PubMed

Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

2016-01-01

Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

Impact of recombination on polymorphism of genes encoding Kunitz-type protease inhibitors in the genus Solanum.

PubMed

Speranskaya, Anna S; Krinitsina, Anastasia A; Kudryavtseva, Anna V; Poltronieri, Palmiro; Santino, Angelo; Oparina, Nina Y; Dmitriev, Alexey A; Belenikin, Maxim S; Guseva, Marina A; Shevelev, Alexei B

2012-08-01

The group of Kunitz-type protease inhibitors (KPI) from potato is encoded by a polymorphic family of multiple allelic and non-allelic genes. The previous explanations of the KPI variability were based on the hypothesis of random mutagenesis as a key factor of KPI polymorphism. KPI-A genes from the genomes of Solanum tuberosum cv. Istrinskii and the wild species Solanum palustre were amplified by PCR with subsequent cloning in plasmids. True KPI sequences were derived from comparison of the cloned copies. "Hot spots" of recombination in KPI genes were independently identified by DnaSP 4.0 and TOPALi v2.5 software. The KPI-A sequence from potato cv. Istrinskii was found to be 100% identical to the gene from Solanum nigrum. This fact illustrates a high degree of similarity of KPI genes in the genus Solanum. Pairwise comparison of KPI A and B genes unambiguously showed a non-uniform extent of polymorphism at different nt positions. Moreover, the occurrence of substitutions was not random along the strand. Taken together, these facts contradict the traditional hypothesis of random mutagenesis as a principal source of KPI gene polymorphism. The experimentally found mosaic structure of KPI genes in both plants studied is consistent with the hypothesis suggesting recombination of ancestral genes. The same mechanism was proposed earlier for other resistance-conferring genes in the nightshade family (Solanaceae). Based on the data obtained, we searched for potential motifs of site-specific binding with plant DNA recombinases. During this work, we analyzed the sequencing data reported by the Potato Genome Sequencing Consortium (PGSC), 2011 and found considerable inconsistence of their data concerning the number, location, and orientation of KPI genes of groups A and B. The key role of recombination rather than random point mutagenesis in KPI polymorphism was demonstrated for the first time. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

PubMed

Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

2016-01-01

Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

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.

Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, L.C.; Tseng, J.C.; Hua, C.C.

2006-03-15

The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes ofmore » these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.« less

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

PubMed

Takemoto, Y; Sakatani, M; Takami, S; Tachibana, T; Higaki, J; Ogihara, T; Miki, T; Katsuya, T; Tsuchiyama, T; Yoshida, A; Yu, H; Tanio, Y; Ueda, E

1998-06-01

Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

PubMed

Quek, S C; Low, P S; Saha, N; Heng, C K

2006-11-01

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

PubMed

Nohara, Hiroaki; Saito, Yuki; Higaki, Singo; Okayama, Naoko; Hamanaka, Yuichiro; Okita, Kiwamu; Hinoda, Yuji

2002-11-01

Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.

PubMed

El Shabrawy, Reham M; Atta, Amal H; Rashad, Nearmeen M

2016-01-01

Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of population worldwide. A key feature of autoimmune thyroiditis is the presence of anti TPO antibodies, and some mutation of the TPO gene. Association between autoimmune thyroiditis and other autoimmune disorders has been reported but little is known about association with allergic diseases. In this study, we aimed to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and examine possible relationship between anti-TPO levels and polymorphism at the TPO gene A2173/C exon 12 and different types of allergens. The study included 50 adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50 controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4) and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti-TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was analyzed using restriction fragment length polymorphism (RFLP). Skin prick test was done to assess allergic response in patients. Serum levels of T3, T4 and TSH did not show any statistical significant difference between patients and groups. However, mean serum anti-TPO level was statistically higher in patients than controls, and correlated positively with body mass index, age, diastolic blood pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in allergic patients than in control group. 2173A>C Genotyping revealed that the frequency of C allele is increased in the patient group. C allele represents a risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05. It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor for developing autoimmune thyroiditis in patients with allergic rhinitis and asthma and that these patients should regularly be checked for hidden thyroiditis. Copyright© by

Transforming growth factor beta-1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case-control study.

PubMed

Khani, Masood; Amani, Davar; Taheripanah, Robabeh; Sanadgol, Nima; Feizollahzadeh, Sadegh; Rahmani, Zahra

2015-10-01

Pre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls. In this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique. At positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P=0.3 and P=0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P=0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P=0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73ng/ml) in PE patients compared with pregnant (47.01ng/ml) and non-pregnant (40.68ng/ml) control groups (P=0.0001). The results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

PubMed Central

Sun, Xudong; Xu, Yuanyuan; Wang, Li; Zhang, Fuhua; Zhang, Jinhua; Fu, Ximei; Jing, Tao; Han, Jian

2016-01-01

Background Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. Methods Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). Results A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. Conclusion Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. PMID:26815578

[Association of polymorphisms in toll-like receptor genes with atopic dermatitis in the Republic of Bashkortostan].

PubMed

Gimalova, G F; Karunas, A S; Fedorova, Iu Iu; Gumennaia, É R; Levasheva, S V; Khismatullina, Z R; Prans, E; Koks, S; Étkina, É I; Khusnutdinova, É K

2014-01-01

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease developing as a result of the interaction between genetic predisposition and environmental factors. Considerable role in allergic diseases development is played by polymorphisms of genes of pattern-recognition receptors (PRR) which are capable of recognizing conservative standard molecular structures (patterns) unique for large pathogen groups. In this study polymorphic variants of PRR genes--Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, TLR10), NOD-like receptors (NOD1, NOD2), lipopolysaccharide receptor CD14 gene, and C11orf30 and LRRC32 genes, located in 11q13.5 region, have been investigated in AD patients and control subjects from the Republic of Bashkortostan. An association of TLR1 (rs5743571 and rs5743604), TLR6 (rs5743794) and TLR10 (rs11466617) with AD was found. Our results confirm an important role of the innate immune system in the pathogenesis of AD and the significance of polymorphisms within the Toll-like receptor 2 subfamily genes in AD development.

RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy.

PubMed

Kaufman, Beth D; Auerbach, Scott; Reddy, Sushma; Manlhiot, Cedric; Deng, Liyong; Prakash, Ashwin; Printz, Beth F; Gruber, Dorota; Papavassiliou, Dimitrios P; Hsu, Daphne T; Sehnert, Amy J; Chung, Wendy K; Mital, Seema

2007-12-01

Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z-scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM.

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

PubMed Central

Ibeagha-Awemu, Eveline M.; Kgwatalala, Patrick; Ibeagha, Aloysius E.

2008-01-01

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 × pathogen × 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. PMID:18350334

[Association of vitamin D receptor gene polymorphisms with mild cognitive impairment among elderly ethnic Uygurs].

PubMed

Zhou, Xiaohui; Zhu, Meisheng; Ma, Li; Miao, Haijun

2015-12-01

To assess the association of vitamin D receptor gene (VDR) Apa I, Bsm I genotypes and allele frequencies and mild cognitive impairment (MCI) among elderly ethnic Uygurs from Xinjiang, China. The polymorphisms of the VDR genotypes (Apa I and Bsm I) were analyzed by the SNaPshot method in 124 MCI patients and 124 controls. Factors which can increase the risk for MCI have included the A allele of the Apa I polymorphism [OR=1.62, 95%CI(1.13-2.31)] and the AA genotype [OR=3.49, 95% CI(1.57-7.74)], the T allele of the Bsm I polymorphism [OR=1.94, 95%CI(1.24-3.05)], higher triglyceride and systolic blood pressure levels. Polymorphisms of the VDR gene including the A allele and AA genotype of Apa I, and the T allele of Bsm I are probably associated with MCI among elderly ethnic Uygurs, and so are higher levels of triglyceride and systolic blood pressure.

New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

PubMed

Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

2017-07-01

The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vitamin D receptor gene Alw I, Fok I, Apa I, and Taq I polymorphisms in patients with urinary stone.

PubMed

Seo, Ill Young; Kang, In-Hong; Chae, Soo-Cheon; Park, Seung Chol; Lee, Young-Jin; Yang, Yun Sik; Ryu, Soo Bang; Rim, Joung Sik

2010-04-01

To evaluate vitamin D receptor (VDR) gene polymorphisms in Korean patients so as to identify the candidate genes associated with urinary stones. Urinary stones are a multifactorial disease that includes various genetic factors. A normal control group of 535 healthy subjects and 278 patients with urinary stones was evaluated. Of 125 patients who presented stone samples, 102 had calcium stones on chemical analysis. The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism analysis. Allelic and genotypic frequencies were calculated to identify associations in both groups. The haplotype frequencies of the VDR gene polymorphisms for multiple loci were also determined. For the VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms, there was no statistically significant difference between the patients with urinary stones and the healthy controls. There was also no statistically significant difference between the patients with calcium stones and the healthy controls. A novel haplotype (Ht 4; CTTT) was identified in 13.5% of the patients with urinary stones and in 8.3% of the controls (P = .001). The haplotype frequencies were significantly different between the patients with calcium stones and the controls (P = .004). The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms does not seem to be candidate genetic markers for urinary stones in Korean patients. However, 1 novel haplotype of the VDR gene polymorphisms for multiple loci might be a candidate genetic marker. Copyright 2010 Elsevier Inc. All rights reserved.

Polymorphisms at the Ligand Binding Site of the Vitamin D Receptor Gene and Osteomalacia

PubMed Central

Ak, Duygu Gezen; Kahraman, Hakkí; Dursun, Erdinç; Duman, Belgin Süsleyici; Erensoy, Nevin; Alagöl, Faruk; Tanakol, Refik; Yılmazer, Selma

2005-01-01

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08). Also no association between biochemical data and VDR gene polymorphisms was observed. PMID:16403954

[Association between VDR gene polymorphisms and HOMA index for prediabetes in Ningxia].

PubMed

Liao, Sha; He, Jun; Li, Xiaoxia; Xu, Honexia; Liu, Xiuying; Zhao, Yi; Zhang, Yuhong

2016-03-01

To explore the association between the vitamin D receptor (VDR) gene polymorphisms and HOMA index in prediabetes. On the basis of a cross-sectional study which was conducted in Ningxia during 2008-2012, 339 controls and 468 subjects with prediabetes were selected according to ADA diabetes diagnosis standards. Anthropometric data and blood samples were collected in the field investigation. Blood biochemistry analyses and insulin determination were carried out in the laboratory. The whole blood DNA was extracted for genotyping. The BMI, WC, FPG and HOMA-IR of individuals with prediabetes were higher than those of the controls, while the HOMA-B and HOMA-S in cases were lower than those of the controls (P < 0.05). In BsmI, individuals with prediabetes carrying genotype BB/Bb showed lower HOMA-B than bb carrier, and they showed significantly higher HOMA-S than bb carriers (P < 0.05). After adjusting age, sex, BMI, TC, TG and SBP, low level HOMA-B index was the risk factor of prediabetes in individuals who carried genotype BB/Bb for BsmI and genotype FF/Ff/ff for FokI (OR > 1 , P < 0.05 ), and the genotype ff got the highest risk level (OR = 10.59). In FokI, the Ff carriers with low level HOMA-S and HOM-IR were also the risk factors of prediabetes (OR > 1, P < 0.05). The VDR gene polymorphisms appeared to be associated with HOMA index in prediabetes. The BsmI polymorphism seemed to influence HOMA-B, while the FokI polymorphism influence HOMA-B and HOMA-IR at different levels.

Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants.

PubMed

Ito, Koichi; Goto, Kenji; Sugiura, Tokio; Muramatsu, Kanji; Ando, Toshihiro; Maniwa, Hiroko; Yokoyama, Takao; Sugiyama, Kohachiro; Togari, Hajime

2007-01-01

Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest. This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.

Association of SNP and STR polymorphisms of insulin-like growth factor 2 receptor (IGF2R) gene with milk traits in Holstein-Friesian cows.

PubMed

Dux, Marta; Muranowicz, Magdalena; Siadkowska, Eulalia; Robakowska-Hyżorek, Dagmara; Flisikowski, Krzysztof; Bagnicka, Emilia; Zwierzchowski, Lech

2018-05-01

The objective of the study reported in this Research Communication was to investigate the association of polymorphisms in the insulin-like growth factor receptor 2 (IGF2R) gene with milk traits in 283 Polish Holstein-Friesian (PHF) cows from the IGAB PAS farm in Jastrzębiec. IGF2R regulates the availability of biologically active IGF2 which is considered as a genetic marker for milk or meat production in farm animals. Two novel genetic polymorphisms were identified in the bovine IGF2R gene: a polymorphic TG-repeat in intron 23 (g.72389 (TG)15-67), and a g.72479 G > A SNP RFLP-StyI in exon 24. The following milk traits were investigated: milk yield, protein and fat yield, SCC and lactose content. To determine the influence of the IGF2R STR and SNP genotypes on the milk traits, we used the AI-REML (average information restricted maximum likelihood) method with repeatability, multi-trait animal model based on test-day information using DMU package. Statistical analysis revealed that the G/A genotype (P ≤ 0·01) was associated with milk and protein yield, lactose content and somatic cell count (SCC) in Polish HF cows. TGn (29/22, 28/29, 28/22, 28/28) genotypes were associated with high values for milk, (28/22, 28/23) with protein and fat yield, (25/20) with lactose content, and (29/33, 28/28) with low SCC. We suggest that the IGF2R gene polymorphisms could be useful genetic markers for dairy production traits in cattle.

No association between apolipoprotein E or N-acetyltransferase 2 gene polymorphisms and age-related hearing loss.

PubMed

Dawes, Piers; Platt, Hazel; Horan, Michael; Ollier, William; Munro, Kevin; Pendleton, Neil; Payton, Antony

2015-01-01

Age-related hearing loss has a genetic component, but there have been limited genetic studies in this field. Both N-acetyltransferase 2 and apolipoprotein E genes have previously been associated. However, these studies have either used small sample sizes, examined a limited number of polymorphisms, or have produced conflicting results. Here we use a haplotype tagging approach to determine association with age-related hearing loss and investigate epistasis between these two genes. Candidate gene association study of a continuous phenotype. We investigated haplotype tagging single nucleotide polymorphisms in the N-acetyltransferase 2 gene and the presence/absence of the apolipoprotein E ε4 allele for association with age-related hearing loss in a cohort of 265 Caucasian elderly volunteers from Greater Manchester, United Kingdom. Hearing phenotypes were generated using principal component analysis of the hearing threshold levels for the better ear (severity, slope, and concavity). Genotype data for the N-acetyltransferase 2 gene was obtained from existing genome-wide association study data from the Illumina 610-Quadv1 chip. Apolipoprotein E genotyping was performed using Sequenom technology. Linear regression analysis was performed using Plink and Stata software. No significant associations (P value, > 0.05) were observed between the N-acetyltransferase 2 or apolipoprotein E gene polymorphisms and any hearing factor. No significant association was observed for epistasis analysis of apolipoprotein E ε4 and the N-acetyltransferase 2 single nucleotide polymorphism rs1799930 (NAT2*6A). We found no evidence to support that either N-acetyltransferase 2 or apolipoprotein E gene polymorphisms are associated with age-related hearing loss in a cohort of 265 elderly volunteers. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population.

PubMed

Abbas, Shania; Raza, Syed Tasleem; Chandra, Anu; Rizvi, Saliha; Ahmed, Faisal; Eba, Ale; Mahdi, Farzana

2015-01-01

Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

Opsin gene polymorphism predicts trichromacy in a cathemeral lemur.

PubMed

Veilleux, Carrie C; Bolnick, Deborah A

2009-01-01

Recent research has identified polymorphic trichromacy in three diurnal strepsirrhines: Coquerel's sifaka (Propithecus coquereli), black and white ruffed lemurs (Varecia variegata), and red ruffed lemurs (V. rubra). Current hypotheses suggest that the transitions to diurnality experienced by Propithecus and Varecia were necessary precursors to their independent acquisitions of trichromacy. Accordingly, cathemeral lemurs are thought to lack the M/L opsin gene polymorphism necessary for trichromacy. In this study, the M/L opsin gene was sequenced in ten cathemeral blue-eyed black lemurs (Eulemur macaco flavifrons). This analysis identified a polymorphism identical to that of other trichromatic strepsirrhines at the critical amino acid position 285 in exon 5 of the M/L opsin gene. Thus, polymorphic trichromacy is likely present in at least one cathemeral Eulemur species, suggesting that strict diurnality is not necessary for trichromacy. The presence of trichromacy in E. m. flavifrons suggests that a re-evaluation of current hypotheses regarding the evolution of strepsirrhine trichromacy may be necessary. Although the M/L opsin polymorphism may have been independently acquired three times in the lemurid-indriid clade, the distribution of opsin alleles in lemurids and indriids may also be consistent with a common origin of trichromacy in the last common ancestor of either the lemurids or the lemurid-indriid clade. (c) 2008 Wiley-Liss, Inc.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

PubMed Central

Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

1998-01-01

BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken.
METHODS—ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2 ) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls.
RESULTS—There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis.
CONCLUSIONS—The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

 PMID:9713444

MBL, P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia.

PubMed

Somuk, Battal Tahsin; Koc, Sema; Ates, Omer; Göktas, Göksel; Soyalic, Harun; Uysal, Ismail Onder; Gurbuzler, Levent; Sapmaz, Emrah; Sezer, Saime; Eyibilen, Ahmet

2016-11-01

A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4 G/C) and MBL2 C + 4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia. This study aimed to investigate the relationship of SLC11A1, MBL, and P2X 7 gene polymorphism with oropharyngeal tularemia. The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5'(GT) n Allele 2/3, Int4 G/C, 3' UTR, D543N G/A), MBL (MBL2 C + 4T (P/Q), and P2X 7 (-762 C/T and 1513 A/C). Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p = 0.006 and OR = 1.96 (1.21-3.20)). An association was detected between MBL2 C + 4T (P/Q) gene polymorphism and oropharyngeal tularemia (p < 0.005 and OR = 0.30 (0.19-0.48)). No significant relation was found between P2X 7 (-762 C/T and 1513 A/C) gene polymorphism and oropharyngeal tularemia in this study (p > 0.05).

Lipid regulatory genes polymorphism in children with and without obesity and cardiometabolic risk factors: The CASPIAN-III study

PubMed Central

Hovsepian, Silva; Javanmard, Shaghayegh Haghjooy; Mansourian, Marjan; Hashemipour, Mahin; Tajadini, Mohamadhasan; Kelishadi, Roya

2018-01-01

Background: Genetically, predisposed children are considered as at-risk individuals for cardiovascular disease. In this study, we aimed to compare the frequency of four-lipid regulatory polymorphism in obese and normal-weight children with and without cardiometabolic risk factors. Materials and Methods: In this nested case–control study, 600 samples of four groups of participants consisted of those with normal weight with and without cardiometabolic risk factors and obese with and without cardiometabolic risk factors. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were compared in the four studied groups. Results: Data of 528 samples were complete and included in this study. The mean (standard deviation) age of participants was 15.01 (2.21) years. Frequency of tt allele (minor allele) of GCKR (rs1260333) polymorphism was significantly lower in normal weight metabolically healthy participants than metabolically unhealthy normal weight (MUHNW) and obese children with and without cardiometabolic risk factor (P = 0.01). Frequency of ga allele of GCKR (rs780094) polymorphism was significantly higher in normal weight children with cardiometabolic risk factor than in their obese counterparts with cardiometabolic risk factor (P = 0.04). Frequency of cg and gg alleles (minor type) of MLXIPL (rs3812316) polymorphism in normal weight metabolically healthy participants was significantly higher than MUHNW (P = 0.04) and metabolically healthy obese children (P = 0.04). Conclusion: The findings of our study indicated that the minor allele of GCKR (rs1260333) single nucleotide polymorphisms (SNPs) could have pathogenic effect for obesity and cardiometabolic risk factors. Ga allele of GCKR (rs780094) SNPs had a protective effect on obesity. Minor alleles of MLXIPL (rs3812316) could have a protective effect for obesity and cardiometabolic risk factors. PMID:29531563

[Association between the methylenetetrahydrofolate reductase gene polymorphisms and haplotype with toxicity response of high dose methotrexate chemotherapy].

PubMed

Liao, Qing-Chuan; Li, Xiao-Lei; Liu, Si-Ting; Zhang, Yong; Li, Tian-Yuan; Qiu, Jin-Chun

2012-07-01

To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL). HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study. The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria. Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 SNP (677C > T and 1298A > C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism. Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program. The distribution of MTHFR gene 677C > T polymorphism did not appeare different between groups with or without toxicity response (χ(2) = 4.609, P = 0.100), but the 1298A > C polymorphism was significantly different (χ(2) = 10.192, P = 0.006). Individuals who carried C allele (AC + CC genotype) had a decreased risk of toxicity response compared to AA genotype (OR = 0.245, 95%CI: 0.099 - 0.607, P = 0.002). 677C > T and 1298A > C polymorphisms showed strong linkage disequilibrium (D' = 0.895). The CC haplotype was significantly associated with decreased risk of toxicity response (OR = 0.338, 95%CI: 0.155 - 0.738, P = 0.005), while the TA haplotype was significantly associated with the increased risk of toxicity response (OR = 1.907, 95%CI: 1.045 - 3.482, P = 0.035). MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.

Interaction between serotonin transporter and serotonin receptor 1 B genes polymorphisms may be associated with antisocial alcoholism.

PubMed

Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Chen-Lin; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

2012-07-11

Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism's heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n=120) and antisocial non-alcoholism (AS-N-ALC) group (n=153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan's Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

Association study of ghrelin receptor gene polymorphisms in rheumatoid arthritis.

PubMed

Robledo, G; Rueda, B; Gonzalez-Gay, M A; Fernández, B; Lamas, J R; Balsa, A; Pascual-Salcedo, D; García, A; Raya, E; Martín, J

2010-01-01

Ghrelin is a newly characterised growth hormone (GH) releasing peptide widely distributed that may play an important role in the regulation of metabolic balance in inflammatory diseases such as rheumatoid arthritis (RA) by decreasing the pro-inflammatory Th1 responses. In this study we investigated the possible contribution of several polymorphisms in the functional Ghrelin receptor to RA susceptibility. A screening of 3 single nucleotide polymorphisms (SNPs) was performed in a total of 950 RA patients and 990 healthy controls of Spanish Caucasian origin. Genotyping of all 3 SNPs was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed no statistically significant deviation between RA patients and controls for the GHSR SNPs analysed. In addition, we performed a haplotype analysis that did not reveal an association with RA susceptibility. The stratification analysis for the presence of shared epitope (SE), rheumatoid factor (RF) or antibodies anti cyclic citrullinated peptide (anti-CCP) did not detect significant association of the GHSR polymorphisms with RA. These findings suggest that the GHSR gene polymorphisms do not appear to play a major role in RA genetic predisposition in our population.

Association of ACE gene A2350G and I/D polymorphisms with essential hypertension in the northernmost province of China.

PubMed

Sun, Feifei; He, Ning; Zhang, Keyong; Wu, Nan; Zhao, Jingbo; Qiu, Changchun

2018-01-01

Angiotensin converting enzyme (ACE) gene, as a strong candidate gene for essential hypertension(EH), has been extensively studied. In this study, we carried out a population-based case-control study to explore whether ACE gene I/D and A2350G polymorphisms could consider to be risk factors for EH. A total of 2040 subjeces were recruited from Chinese Han in this study, out of which 1010 were cases and 1030 were normotensive individuals. ACE gene A2350G and I/D polymorphisms were amplified by polymerase chain reaction (PCR) and A2350G polymorphism was detected after restriction enzyme digestion with BstuI. Besides, we choosed 10% samples randomly sequencing to verify the accuracy of results. Genotype and allele frequencies distribution of I/D and A2350G in EH and control groups were significantly different. After grouped by sex or age, there were still statistical significances for two polymorphisms. In dominant and recessive model of A2350G, we found significant differences between two groups, respectively. For ACE I/D polymorphism, we observed that the existence of dramatical difference in dominant model between two groups, while in recessive model, marginally significant difference was found. Among the four haplotypes composed by ACE gene A2350G and I/D, haplotype G-D reached the statistical significance in two groups, and exhibited to be a risk factor for the development of EH, whose P < 0.001 and OR 95%CI = 1.639(1.435-1.872), while the other haplotypes were the protective factors and decreased the susceptibility to EH(P < 0.05). ACE gene A2350G and I/D polymorphisms were associated with increasing the risk of suffering from EH in the northernmost province of China individuals, with D allele and G allele individuals had a higher risk of EH(OR = 1.443, 95%CI = 1.273-1.636 and OR = 1.481, 95%CI = 1.303-1.684).

Analysis of -1082 IL-10 gene polymorphism in Iranian patients with generalized aggressive periodontitis.

PubMed

Mellati, Ehsan; Arab, Hamid R; Tavakkol-Afshari, Jalil; Ebadian, Ahmad R; Radvar, Mehrdad

2007-11-01

Periodontitis is a multifactorial disease and its severe forms, such as aggressive periodontitis, are suggested to have a genetic basis. Among the genetic factors, polymorphisms in cytokine genes have recently been described in susceptibility to periodontitis. IL-10 is a multi-functional cytokine thought to play a role in the pathogenesis of periodontitis. A substitution G/A polymorphism in the promoter region of the IL-10 gene at position -1082 has been associated with different amounts of IL-10 production. The aim of the present study was to investigate the possible links between -1082(G/A) polymorphism of the IL-10 gene and the generalized form of aggressive periodontitis. This study included 52 Iranian Khorasanian (north-east province of Iran) subjects suffering from generalized aggressive periodontitis referred to the Periodontology Department of Mashhad Dental School. They were compared to 61 age and sex-matched healthy controls of the same race. DNA was isolated from peripheral blood cells and genotyping was performed by means of the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Data were analyzed using the chi-squared test. There was no marked difference in genotype frequencies between the controls and generalized aggressive periodontitis patients (p=0.585). Moreover, no association between patients and normal subjects was found in their allele frequency (p=0.329). We conclude that the polymorphic nucleotide A at position -1082 of the IL-10 gene is not associated with generalized aggressive periodontitis in the Iranian population.

Associations between single nucleotide polymorphisms in multiple candidate genes and body weight in rabbits

PubMed Central

El-Sabrout, Karim; Aggag, Sarah A.

2017-01-01

Aim: In this study, we examined parts of six growth genes (growth hormone [GH], melanocortin 4 receptor [MC4R], growth hormone receptor [GHR], phosphorglycerate mutase [PGAM], myostatin [MSTN], and fibroblast growth factor [FGF]) as specific primers for two rabbit lines (V-line, Alexandria) using nucleotide sequence analysis, to investigate association between detecting single nucleotide polymorphism (SNP) of these genes and body weight (BW) at market. Materials and Methods: Each line kits were grouped into high and low weight rabbits to identify DNA markers useful for association studies with high BW. DNA from blood samples of each group was extracted to amplify the six growth genes. SNP technique was used to study the associate polymorphism in the six growth genes and marketing BW (at 63 days) in the two rabbit lines. The purified polymerase chain reaction products were sequenced in those had the highest and lowest BW in each line. Results: Alignment of sequence data from each group revealed the following SNPs: At nucleotide 23 (A-C) and nucleotide 35 (T-G) in MC4R gene (sense mutation) of Alexandria and V-line high BW. Furthermore, we detected the following SNPs variation between the two lines: A SNP (T-C) at nucleotide 27 was identified by MC4R gene (sense mutation) and another one (A-C) at nucleotide 14 was identified by GHR gene (nonsense mutation) of Alexandria line. The results of individual BW at market (63 days) indicated that Alexandria rabbits had significantly higher BW compared with V-line rabbits. MC4R polymorphism showed significant association with high BW in rabbits. Conclusion: The results of polymorphism demonstrate the possibility to detect an association between BW in rabbits and the efficiency of the used primers to predict through the genetic specificity using the SNP of MC4R. PMID:28246458

Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W.

1994-06-01

Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragmentmore » length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.« less

Tumor necrosis factor-α -308 G/A and interleukin 10 -1082 A/G gene polymorphisms in patients with acne vulgaris.

PubMed

Al-Shobaili, Hani A; Salem, Tarek A; Alzolibani, Abdullateef A; Robaee, Ahmad Al; Settin, Ahmad A

2012-10-01

Cytokines play an important role in the pathogenesis of acne vulgaris together with other genetic and environmental factors. To check for the association of TNF-α and IL-10 gene polymorphisms with the susceptibility and severity of acne in Saudi patients. Study subjects included 166 Saudi patients (65 males, 101 females) with acne vulgaris. Their mean age±SD was 21.6±5.1 years. These cases were compared to 390 unrelated healthy controls (208 males, 182 females) with a mean age±SD of 20.1±3.3 years. Cases were sub-grouped on the basis of their severity of acne affection into mild, moderate and severe groups. For all participants, genotypic variants of the TNF-α -308 G/A and IL-10 -1082 A/G genes were determined using the real time PCR technique. Frequencies of genotypic variants of the TNF-α -308 polymorphism were significantly different in acne cases compared to controls. Further analysis showed that acne cases had significantly higher frequency of both the GG and AA homozygous forms than controls (73.8% vs. 63.6%, p=0.02, odds ratio=1.6). It was also interestingly noticed that the amount of GG homozygosity was notably higher among female cases than male ones (76.0% vs. 54.7%, p=0.006, odds ratio=2.6) whereas male cases had a higher frequency of AA and GA genotypes than female ones (9.4% and 35.9% vs. 4% and 20% respectively). Differences in the frequencies of IL-10 -1082 genotypic variants were statistically insignificant comparing cases to controls (p=0.3). On the other hand, comparing cases-subgroups in terms of the age of onset of the disease, consanguinity, family history, obesity and acne severity; no statistical significance was observed regarding frequencies of genotypic variants related to the both TNF-α -308 and IL-10 -1082 polymorphisms (>0.05). TNF-α -308 polymorphic variants might be a predisposing factor for acne susceptibility, with no apparent relation to its severity whereas IL-10 -1082 variants showed no association with both acne

Paraoxonase gene Q192R & L55M polymorphisms in Indians with acute myocardial infarction & association with oxidized low density lipoprotein.

PubMed

Lakshmy, Ramakrishnan; Ahmad, Dilawar; Abraham, Rani Ann; Sharma, Mukta; Vemparala, Kranthi; Das, Siuli; Reddy, K Srinath; Prabhakaran, Dorairaj

2010-04-01

Paraoxonase (PON) is an HDL associated ester hydrolase with an ability to retard LDL oxidation in vitro by preventing lipid peroxide generation. The population variability in enzyme activity is attributed to polymorphisms in paraoxonase gene. For example, polymorphism at codon 192 and 55 of the paraoxonase gene has been reported to be associated with coronary heart disease (CAD) and diabetes among different ethnic groups. The present study looks at PON192 and 55 polymorphism among hospitalized Asian Indian patients with myocardial infarction (MI) and their association with circulating oxidized LDL and antioxidant status. One hundred and twenty four consecutive patients of acute myocardial infarction and 221 age-matched controls were recruited for the study. Oxidized LDL was measured in serum by ELISA and total antioxidant levels by the 2,2'-azino-bis-(3 ethyl benzothiozoline-6-sulfonate) (ABTS) method. Other known cardiovascular risk factors, apolipoprotein B, apolipoproteinA1, lipoprotein(a), hsCRP and homocysteine were also measured. Paraoxonase gene polymorphism at codon 192 and 55 were analyzed by PCR-RFLP. Patients with MI had significantly higher oxidized LDL (P<0.05) and lower total antioxidant capacity (P<0.001) as compared to controls. Oxidized LDL correlated with total cholesterol, LDL and Apo B in patients. B allele frequency of the codon 192 polymorphism in paraoxonase gene was higher in cases as compared to controls and odds ratio of developing the MI with BB genotype versus AA genotype was 2.37, (P=0.044). Codon 55 polymorphism in paraoxonase gene was not associated with CAD. There was no difference in oxidized LDL between the different genotypes of PON192 and PON55. Although PON192 polymorphism was associated with CAD, no correlation of PON192 or 55 polymorphism was found with oxidized LDL suggesting that presence of other antioxidant factors may be of equal importance in preventing LDL oxidation.

Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

PubMed Central

Butovskaya, Marina L.; Lazebny, Oleg E.; Vasilyev, Vasiliy A.; Dronova, Daria A.; Karelin, Dmitri V.; Mabulla, Audax Z. P.; Shibalev, Dmitri V.; Shackelford, Todd K.; Fink, Bernhard; Ryskov, Alexey P.

2015-01-01

The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

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.

Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP

PubMed Central

Azab, Seham F.; Abdalhady, Mohamed A.; Elsaadany, Hosam F.; Elkomi, Mohamed A.; Elhindawy, Eman M.; Sarhan, Dina T.; Salam, Mohamed M.A.; Allah, Mayy A.N.; Emam, Ahmed A.; Noah, Maha A.; Abdelsalam, Nasser I.; Abdellatif, Sawsan H.; Rass, Anwar A.; Ismail, Sanaa M.; Gheith, Tarek; Aziz, Khalid A.; Hamed, Mohammed E.; Abdelrahman, Hind M.; Ahmed, Ahmed R.; Nabil, Rehab M.; Abdulmaksoud, Rehab S.; Yousef, Hala Y.

2016-01-01

Abstract Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP. In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism. This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method. Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01). We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis

Interleukin-6 level and gene polymorphism in spontaneous miscarriage.

PubMed

Drozdzik, M; Szlarb, N; Kurzawski, M

2013-09-01

The aetiology of spontaneous miscarriage, the most common pregnancy complication, remains undefined. One of postulated factors involved in miscarriage pathology is interleukin 6 (IL-6). Therefore, the aim of the study was to evaluate IL-6 and interleukin 6 receptor (IL-6R) gene polymorphisms in patients with spontaneous miscarriage. One hundred fifty-seven patients diagnosed with spontaneous miscarriage and age and gestational time matched controls were included in the case-control study. In all study participants circulating IL-6 levels (chemiluminescent immunoassay) and IL6-174G>C as well as IL6R rs2228145:A>C polymorphisms were evaluated. The distribution of IL6 as well as IL6R alleles and genotypes were similar in the controls and patients with miscarriage. Only a trend of more frequent appearance of -174GC+CC and C allele in the patients with miscarriage was noted. Blood serum concentrations of IL-6 were significantly elevated in patients with miscarriage vs those with physiological pregnancy. Likewise, IL-6 concentrations differ significantly with the types of miscarriage. The highest concentrations of the cytokine was seen in subjects with incomplete miscarriage (4.28 ± 4.88 pg/ml) followed by imminent miscarriage (2.97 ± 2.42 pg/ml), and then missed miscarriage (2.07 ± 1.90 pg/ml), being significantly the lowest in missed miscarriage group. No association between the IL6 genotype and IL-6 serum concentration were noted, both in the miscarriage group and in the control group. The findings of the study support the role of IL-6 in spontaneous miscarriage irrespectively of its type. However, no correlation between circulating IL-6 and IL6 gene polymorphism, as well as IL-6 and IL-6R polymorphisms associations with spontaneous miscarriage were revealed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Meta-analysis of association of tumor necrosis factor alpha-308 gene promoter polymorphism with gastric cancer].

PubMed

Lu, Pei-hua; Tang, Yun; Li, Chen; Shen, Wei; Ji, Lü; Guo, Yu-jiang; Tao, Guo-qing

2010-03-01

To assess the association between tumor necrosis factor-alpha (TNF-alpha) gene promoter region -308 gene polymorphisms and gastric cancer (GC) susceptibility. Published work about TNF-alpha-308 and GC from PubMed, EMBASE, Cochrane library in English and from Wanfang, CBM in Chinese were searched for relevant articles published by the end of July, 2009. Thirty-nine relevant articles were selected and 26 of them met the criteria. The correlated index was extracted for aggregate analysis in RevMan 4.2. There were 5225 GC patients and 8473 controls for TNF-alpha-308 in 26 papers. Overall, allele contrast (G:A and AA:GG) genotype of TNF-alpha-308 polymorphisms produced significant results in worldwide populations, the OR values were 0.85 (95%CI: 0.76 - 0.96, P = 0.01) and 1.19 (95%CI: 1.01 - 1.39, P = 0.03). Subgroup analysis showed that OR values of G:A and AA:GG in west population were 0.79 (95%CI: 0.70 - 0.89, P < 0.01) and 1.26 (95%CI: 1.04 - 1.52, P = 0.02), while in east populations subgroup analysis, the OR was 0.97 (95%CI: 0.75 - 1.26, P = 0.84). No significant association was observed in non-cardia GC and Helicobacter pylori positive GC, the OR values were 0.90 (95%CI: 0.79 - 1.02, P = 0.10) and 1.08 (95%CI: 0.62 - 1.88, P = 0.79). TNF-alpha-308 A allele and AA genotype were associated with a statistically significant increased risk of gastric cancer in western people.

Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.

PubMed

Kim, Sang-Heon; Kim, Yoon-Keun; Park, Heung-Woo; Jee, Young-Koo; Kim, Sang-Hoon; Bahn, Joon-Woo; Chang, Yoon-Seok; Kim, Seung-Hyun; Ye, Young-Min; Shin, Eun-Soon; Lee, Jong-Eun; Park, Hae-Sim; Min, Kyung-Up

2007-04-01

Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype. We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls). Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: -616C>G (P=0.038) and -166G>A (P=0.023) in PTGER2; -1709T>A (P=0.043) in PTGER3; -1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and -4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015). These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma.

Is the polymorphism at position -1082 of IL-10 gene associated with visceral leishmaniasis?

PubMed

Hajilooi, Mehrdad; Ahmadi, Alireza; Lotfi, Pegah; Matini, Mohammad; Jafari, Davood; Bazmani, Ahad; Momeni, Mohammad

2014-08-01

Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL.

Folate and Breast Cancer: Role of Intake, Blood Levels, and Metabolic Gene Polymorphisms

DTIC Science & Technology

2005-07-01

folate, and metabolic gene polymorphisms in relation to breast cancer risk: Months 1-19. b. Prepare blood samples for relevant assays: Months 1-19... gene polymorphism assays among the 184 cases and matched controls. The folate assays are on-going at this time. DNA assays will commence in the... methotrexate . Ann Oncol 13: 1915–1918, 2002 13. Toffoli G, Veronesi A, Boiocchi M, Crivellari D: MTHFR gene polymorphism and severe toxicity during

The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive Symptoms.

PubMed

Liu, Yangyang

2015-07-01

The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms.

Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality

PubMed Central

Armeni, Anastasia K; Assimakopoulos, Konstantinos; Marioli, Dimitra; Koika, Vassiliki; Michaelidou, Euthychia; Mourtzi, Niki; Iconomou, Gregoris

2017-01-01

Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences. PMID:28069897

[Polymorphism in the regulatory regions -С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis].

PubMed

Shevchenko, A V; Prokofyev, V F; Korolev, M A; Banshchikova, N E; Konenkov, V I

To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

Correlations of CTLA-4 gene polymorphisms and hepatitis C chronic infection.

PubMed

Danilovic, Debora L S; Mendes-Correa, Maria C; Lima, Erika U; Zambrini, Heverton; K Barros, Raffaelle; Marui, Suemi

2012-05-01

Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies. © 2011 John Wiley & Sons A/S.

LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

PubMed

Røsby, O; Berg, K

2000-01-01

In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

p16 gene silencing along with p53 single-nucleotide polymorphism and risk of esophageal cancer in Northeast India.

PubMed

Das, Mandakini; Sharma, Santanu Kumar; Sekhon, Gaganpreet Singh; Mahanta, Jagadish; Phukan, Rup Kumar; Jalan, Bimal Kumar

2017-05-01

The high incidence of esophageal cancer in Northeast India and the unique ethnic background and dietary habits provide a great opportunity to study the molecular genetics behind esophageal squamous cell carcinoma in this part of the region. We hypothesized that in addition to currently known environmental risk factors for esophageal cancer, genetic and epigenetic factors are also involved in esophageal carcinogenesis in Northeast India. Therefore, in this study, we explored the possible association between the two important G1 cell cycle regulatory genes p16 and p53 and environmental risk factors and risk of esophageal carcinogenesis. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age-, sex-, and ethnicity-matched controls were included in this study. Methylation-specific polymerase chain reaction was used to determine the p16 promoter methylation status. Single-nucleotide polymorphism at codon 72 of p53 gene was assessed by the polymerase chain reaction-restriction fragment length polymorphism method. Aberrant methylation of p16 gene was seen in 81% of esophageal cancer cases. Hypermethylation of p16 gene was not found in healthy controls. p53 Pro/Pro genotype was found to be a risk genotype in Northeast India compared with Arg/Pro and Arg/Arg. p53 variant/polymorphism was significantly associated with esophageal cancer risk in the study population under all three genetic models, namely, dominant model (Arg/Pro + Pro/Pro vs Arg/Arg odds ratio = 2.25, confidence interval = 1.19-4.26; p = 0.012), recessive model (Arg/Arg + Arg/Pro vs Pro/Pro odds ratio = 2.35, confidence interval = 1.24-4.44; p = 0.008), and homozygous model (Pro/Pro vs Arg/Arg odds ratio = 3.33, confidence interval = 1.54-7.20; p = 0.002). However, p53 variant/polymorphism was not statistically associated with esophageal cancer risk under the heterozygous model (Pro/Pro vs Arg/Pro). In the case-only analysis based on p16

Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

PubMed

Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

2017-07-01

The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns.

PubMed

Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

1997-01-01

Low basal metabolic rate (BMR) is a risk factor for weight gain and obesity. The polymorphism at codon 64 of the beta3-adrenergic receptor gene has been suggested to be associated with BMR. We investigated the frequency of the Trp64Arg of the beta3-adrenergic receptor gene and the effects of this polymorphism on BMR in obese Finns. Altogether, 170 obese subjects (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m2, mean +/- SD) participated in the study. The frequency of the Trp64Arg polymorphism was 19%. None of the obese subjects were homozygous for the Arg-encoding allele. The frequency of the Trp64Arg polymorphism in obese Finns did not differ from nonobese and normoglycemic control subjects. BMR adjusted for lean body mass and age was lower in subjects with the Trp64Arg polymorphism (n = 20) than in normal homozygotes Trp64Trp (n = 99) (1,569 +/- 73 vs. 1,635 +/- 142 kcal/day, P = 0.004). For the female group (n = 98), the respective values were 1,501 +/- 66 kcal/day vs. 1,568 +/- 127 kcal/day (P = 0.004). There were no significant differences in weight, BMI, waist-to-hip ratio, lean body mass, percentage of fat, and respiratory quotient between the groups with or without the Trp64Arg polymorphism. Neither serum glucose nor insulin levels differed between the two groups. We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns but does not have significant effect on glucose metabolism.

Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population

PubMed Central

Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

2015-01-01

Abstract The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population. A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group). Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model. Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population. PMID:26717388

Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population.

PubMed

Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

2015-12-01

The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population.A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group).Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model.Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population.

Polymorphism analysis of prion protein gene in 11 Pakistani goat breeds

PubMed Central

Hassan, Mohammad Farooque; Khan, Sher Hayat; Babar, Masroor Ellahi; Yang, Lifeng; Ali, Tariq; Khan, Jamal Muhammad; Shah, Syed Zahid Ali; Zhou, Xiangmei; Hussain, Tanveer; Zhu, Ting; Hussain, Tariq; Zhao, Deming

2016-01-01

ABSTRACT The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. PMID:27388702

Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers.

PubMed

Bednarska-Makaruk, Małgorzata; Rodo, Maria; Markuszewski, Cezary; Rozenfeld, Anna; Swiderska, Malgorzata; Habrat, Bogusław; Wehr, Hanna

2005-01-01

To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events.

DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk.

PubMed

Stern, M C; Umbach, D M; van Gils, C H; Lunn, R M; Taylor, J A

2001-02-01

Bladder cancer is the sixth most common cancer in the United States. The main identified risk factor is cigarette smoking, which is estimated to contribute to up to 50% of new cases in men and 20% in women. Besides containing other carcinogens, cigarette smoke is a rich source of reactive oxygen species (ROS) that can induce a variety of DNA damage, some of which is repaired by the base excision repair (BER) pathway. The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single-strand DNA breaks. Three polymorphisms that induce amino acid changes have been found in codon 194 (exon 6), codon 280 (exon 9), and codon 399 (exon 10) of this gene. We tested whether polymorphisms in XRCC1 were associated with bladder cancer risk and whether this association was modified by cigarette smoking. Therefore, we genotyped for the three polymorphisms in 235 bladder cancer cases and 213 controls who had been frequency matched to cases on age, sex, and ethnicity. We found no evidence of an association between the codon 280 variant and bladder cancer risk [odds ratio (OR), 1.2; 95% confidence interval (CI), 0.6-2.6]. We found some evidence of a protective effect for subjects that carried at least one copy of the codon 194 variant allele relative to those homozygous for the common allele (OR, 0.59; 95% CI, 0.3-1.0). The combined analysis with smoking history suggested a possible gene-exposure interaction; however, the results were not statistically significant. Similarly, for the codon 399 polymorphism, our data suggested a protective effect of the homozygous variant genotype relative to carriers of either one or two copies of the common allele (OR, 0.70; 95% CI, 0.4-1.3), and provided limited evidence, albeit not statistically significant, for a gene-smoking interaction.

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

PubMed Central

Hashemi, Mohammad; Hanafi Bojd, Hamideh; Eskandari Nasab, Ebrahim; Bahari, Ali; Hashemzehi, Noor Allah; Shafieipour, Sara; Narouie, Behzad; Taheri, Mohsen; Ghavami, Saeid

2013-01-01

Background Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway. Objectives The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD. Patients and Methods Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms. Results A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697). Conclusions adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations. PMID:23922565

Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia.

PubMed

Dávalos, I P; Moran, M C; Martínez-Abundis, E; González-Ortiz, M; Flores-Martínez, S E; Machorro, V; Sandoval, L; Figuera, L E; Mena, J P; Oliva, J M; Tlacuilo-Parra, J A; Sánchez-Corona, J; Salazar-Páramo, M

2005-01-01

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.

Glypican-4 gene polymorphism (rs1048369) and susceptibility to Epstein-Barr virus-associated and -negative gastric carcinoma.

PubMed

Zhao, Danrui; Liu, Shuzhen; Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Kuang, Xiaojing; Shu, Jun; Luo, Bing

2016-07-15

Gastric cancer (GC) is one of the most common malignant tumors in China and single nucleotide polymorphisms (SNPs) have been found to be highly related to GC carcinogenesis. Glypican-4 (GPC4), a member of the heparan sulphate proteoglycan family, plays an important role in the regulation of cell growth and differentiation. However, little is known about polymorphisms of GPC4 gene and their associated susceptibility to GC, especially to Epstein-Barr virus-associated GC (EBVaGC). Here we studied the GPC4 polymorphism (rs1048369) in GC individuals, especially those with EBVaGC, and we explored an association between the GPC4 gene polymorphism (rs1048369) and susceptibility to EBVaGC and Epstein-Barr virus-negative GC (EBVnGC) in a population from Northern China. The GPC4 gene polymorphism (rs1048369) was detected in 54 cases of EBVaGC and 73 cases of EBVnGC using polymerase chain reaction (PCR). One hundred and seven peripheral blood samples from healthy individuals were also measured as a control group. There were significant differences in both the genotype and allelic frequency of GPC4 gene (rs1048369) between the EBVaGC and EBVnGC patients. Meanwhile, the distribution of genotype and allelic frequency of GPC4 (rs1048369) differed between EBVaGC and control groups. Distribution of the GPC4 genotype also revealed differences between EBVnGC and control groups, no significant differences in the allelic frequency of the GPC4 gene (rs1048369) were observed. The frequency of the T allele in EBVaGC group was significantly higher than that in control and EBVnGC groups. The GPC4 gene polymorphism and the allele of GPC4 are both associated with susceptibility to EBVaGC. The T allele of GPC4 may represent a risk factor for EBVaGC. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia.

PubMed

Forero, Diego A; Benítez, Bruno; Arboleda, Gonzalo; Yunis, Juan J; Pardo, Rodrigo; Arboleda, Humberto

2006-07-01

In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimer's disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brain-derived neurotrophic factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia. There was not association between UCHL1 polymorphism and AD in our sample. We have found an initial association with BDNF polymorphism in familial cases and with COMT polymorphism in male and sporadic patients. These initial associations were lost after Bonferroni correction for multiple testing. Unadjusted results may be compatible with the expected functional effect of variations in these genes on pathological memory and cognitive dysfunction, as has been implicated in animal and cell models and also from neuropsychological analysis of normal subjects carriers of the AD associated genotypes. An exploration of functional variants in these and in other synaptic plasticity-related genes (a synaptogenomics approach) in independent larger samples will be important to discover new genes associated with AD.

Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

PubMed Central

2012-01-01

Background Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan. Methods We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n = 120) and antisocial non-alcoholism (AS-N-ALC) group (n = 153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP. Results There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism. Conclusion Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism. PMID:22550993

Detoxification genes polymorphisms in SIDS exposed to tobacco smoke.

PubMed

Filonzi, Laura; Magnani, Cinzia; Lavezzi, Anna Maria; Vaghi, Marina; Nosetti, Luana; Nonnis Marzano, Francesco

2018-03-30

The best hypothesis to explain Sudden Infant Death Syndrome (SIDS) pathogenesis is offered by the "triple risk model", which suggests that an interaction of different variables related to exogenous stressors and infant vulnerability may lead to the syndrome. Environmental factors are triggers that act during a particular sensible period, modulated by intrinsic genetic characteristics. Although literature data show that one of the major SIDS risk factors is smoking exposure, a specific involvement of molecular components has never been highlighted. Starting from these observations and considering the role of GSTT1 and GSTM1 genes functional polymorphisms in the detoxification process, we analyzed GSTM1 and GSTT1 null genotype frequencies in 47 SIDS exposed to tobacco smoke and 75 healthy individuals. A significant association (p < .0001) between the GSTM1 null genotype and SIDS exposed to smoke was found. On the contrary, no association between GSTT1 polymorphism and SIDS was determined. Results indicated the contribution of the GSTM1 -/- genotype resulting in null detoxification activity in SIDS cases, and led to a better comprehension of the triple risk model, highlighting smoking exposure as a real SIDS risk factor on a biochemical basis. Copyright © 2018. Published by Elsevier B.V.

[Correlation between polymorphisms in the coagulation factor VII gene hypervariable region 4 site and the risk of coronary heart disease in population with different ethnic backgrounds: a Meta-analysis].

PubMed

Wang, Li-li; Ma, Bin; Qian, Dun; Pang, Jun; Yao, Ya-li

2013-12-01

To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.

Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia.

PubMed

Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Heidari, Farzad; Haghvirdizadeh, Polin; Ataollahi Eshkoor, Sima; Etemad, Ali

2016-01-01

With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation between Ala589Ser polymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p < 0.05). The distribution of allele frequency and genotype of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients.

PubMed

Kucharczyk, Tomasz; Krawczyk, Paweł; Powrózek, Tomasz; Kowalski, Dariusz M; Ramlau, Rodryg; Kalinka-Warzocha, Ewa; Knetki-Wróblewska, Magdalena; Winiarczyk, Kinga; Krzakowski, Maciej; Milanowski, Janusz

2016-01-01

In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.

N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis.

PubMed

Hemanth Kumar, A K; Ramesh, K; Kannan, T; Sudha, V; Haribabu, Hemalatha; Lavanya, J; Swaminathan, Soumya; Ramachandran, Geetha

2017-01-01

Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes.

N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis

PubMed Central

Hemanth Kumar, A. K.; Ramesh, K.; Kannan, T.; Sudha, V.; Haribabu, Hemalatha; Lavanya, J.; Swaminathan, Soumya; Ramachandran, Geetha

2017-01-01

Background & objectives: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. Methods: Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. Results: Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). Interpretation & conclusions: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes. PMID:28574024

Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis

PubMed Central

Das, Shukla; Ramachandran, V.G.; Saha, Rumpa; Bhattacharya, S.N.; Dar, Sajad

2017-01-01

Introduction Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. Aim To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Materials and Methods Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Statistical Analysis Chi-Square Test or Fisher’s-Exact Test and Bonferroni’s correction. Results In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group

Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration.

PubMed

Ambreen, Fareeha; Ismail, Muhammad; Qureshi, Irfan Zia

2015-01-01

To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients. This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box-Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ(2) tests applying Hardy-Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05. Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant alteration in serum CRP levels

A common polymorphism of the MCT1 gene and athletic performance.

PubMed

Fedotovskaya, Olga N; Mustafina, Leysan J; Popov, Daniil V; Vinogradova, Olga L; Ahmetov, Ildus I

2014-01-01

In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79). Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer. Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005). MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.

Genetic Risk Factors for Psoriasis in Turkish Population: -1540 C/A, -1512 Ins18, and +405 C/G Polymorphisms within the Vascular Endothelial Growth Factor Gene

PubMed Central

Bozduman, Tuba; Ersoy Evans, Sibel; Karahan, Sevilay; Hayran, Yildiz; Akbiyik, Filiz

2016-01-01

Background Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. Objective VEGFA gene polymorphisms (-1540 C/A, -1512 Ins18, -460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. Methods A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes. Results The +405 GG, +405 CG, -1540 CA, and -1512 +Ins18 genotypes conferred a significant risk for developing psoriasis. The C-InsTC haplotype in the controls and C+InsTG, A+InsTC, and A-InsTG haplotypes in psoriatic patients were observed to be significantly high. Increased serum levels of VEGFA were detected in psoriatic patients with the C-InsTC haplotype than that in the controls. The +405 GG genotype was significantly more frequent in psoriatic patients with a positive family history, and the moderate form of psoriasis was more frequent among C+InsTG haplotype carriers than that among the other patients. The +405 GG genotype was found to be more frequent in patients responding to oral retinoids. Serum VEGFR1/FLT1 and VEGFR2/KDR levels were not significantly different when psoriatic patients and controls were stratified based on the risk polymorphic variants. Conclusion VEGFA gene +405 GG and CG, -1512+Ins18, and -1540 CA genotypes are associated with an increased risk of psoriasis in Turkish population. The G allele at +405 and an 18-bp insertion at -1512 are primarily the risk factors for psoriasis, and this risk is potentiated by the presence of the A allele at the -1540 locus. PMID:26848216

Association of the glucocorticoid receptor gene polymorphisms and their interaction with stressful life events in Polish adolescent girls with anorexia nervosa.

PubMed

Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Slopien, Agnieszka; Tyszkiewicz, Marta; Maciukiewicz, Malgorzata; Zaremba, Dorota; Twarowska-Hauser, Joanna

2016-03-01

Disturbances in stress response mechanisms and hypothalamic-pituitary-adrenal axis (HPA) functioning are considered important factors involved in the pathophysiology of anorexia nervosa (AN). Thus, genetic variations in the end effector of HPA - glucocorticoid receptor gene and relationships to stressful life events (SLE) may be connected to a higher risk of illness. The aim of the study was examining the association between glucocorticoid receptor gene (NR3C1) polymorphisms and risk factors among stressful life events in AN patients. This study comprised 256 patients with AN and 167 control subjects. The questionnaires examining brief history of the mother's pregnancy and long-acting stress factors, as well as life events checklist to assess stressful life events during the 6 months prior to hospitalization were used. The eight common SNPs (rs6198, rs6191, rs6196, rs258813, rs33388, rs41423247, rs56149945 and rs10052957) of NR3C1 gene were genotyped. The association of five polymorphisms (rs6191, rs258813, rs33388, rs41423247 and rs10052957) and one complex allele (TCAGT) of NR3C1 gene with increased risk of AN were found. However, no significant correlations between early, long-acting and predicting hospitalization SLE and any of the analyzed polymorphisms were observed. The results confirm that the NR3C1 gene is associated with AN risk regardless of the type of stressful triggering factors.

Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

PubMed

Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

2016-12-01

Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interleukin-18 -607C/A gene polymorphism in Egyptian asthmatic children.

PubMed

Shaaban, Hala Hamdi; Mohy, Abeer Mohamed; Abdel-Razek, Abdel-Rahman Ahmed; Wahab, Amira Abdel

2014-08-01

Asthma is a multifactorial respiratory disease determined by interactions of multiple disease susceptibility genes and environmental factors. Interleukin (IL)-18 is an important cytokine for initiating and perpetuating the catabolic and inflammatory response in allergic asthma. A number of single nucleotide polymorphisms that influence IL-18 production are found in the gene promoter region. The aim of this study was to investigate the association of IL-18 -607C/A promoter polymorphism with asthma and whether this polymorphism influenced the severity of asthma in affected children. The influence of this promoter gene polymorphism on total serum IgE level in studied subjects was also investigated. This study was carried out at the Allergy Clinic of Abu El Reesh Children's Hospital at Cairo University, Egypt. This study included 40 asthmatic children, subdivided into four groups according to different degrees of asthma severity, and 20 apparently healthy subjects as the control group. All cases were subjected to history taking, clinical examination, and the following laboratory investigations: complete blood count, total serum IgE level assay by ELISA and genomic DNA extraction, and analysis for IL-18 -607C/A promoter gene polymorphism using the PCR-RFLP (restriction fragment length polymorphism) technique. In the present study the IL-18 -607AA genotype frequency was higher in cases (22.5 %) than in the control group (15 %); however, the difference was not statistically significant (p = 0.773). No statistically significant difference between the degree of asthma severity and IL-18 -607C/A polymorphism was found (p = 0.489). No significant association could be detected upon comparing the frequencies of C and A alleles among the two studied groups (p = 0.366). Also, no significant differences were demonstrated for the allele frequencies when the intermittent with mild [odds ratio (OR) = 2.72, 95 % CI 1.03-2.33, p = 0.067], intermittent with moderate, and severe (OR = 2

Is the Polymorphism at Position -1082 of IL-10 Gene Associated with Visceral Leishmaniasis?

PubMed Central

HAJILOOI, Mehrdad; AHMADI, Alireza; LOTFI, Pegah; MATINI, Mohammad; JAFARI, Davood; BAZMANI, Ahad; MOMENI, Mohammad

2014-01-01

Abstract Background Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). Methods The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. Results The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Conclusions Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL. PMID:25927040

Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes.

PubMed

de Melo, Sandra Fabrico; Frigeri, Henrique Ravanhol; dos Santos-Weiss, Izabella Castilhos Ribeiro; Réa, Rosângela Roginski; de Souza, Emanuel Maltempi; Alberton, Dayane; Gomes de Moraes Rego, Fabiane; Picheth, Geraldo

2015-11-01

To investigate the association between fat mass and obesity-associated (FTO) gene polymorphisms rs8050136C>A and rs9939609T>A, and transcription factor 7-like 2 (TCF7L2) gene polymorphisms rs12255372G>T and rs7903146C>T, in a sample group of pregnant Euro-Brazilian women with or without gestational diabetes mellitus (GDM). Subjects were classified as either healthy pregnant control (n=200) or GDM (n=200) according to the 2010 criteria of the American Diabetes Association. The polymorphisms were genotyped using fluorescent probes (TaqMan®). All groups were in the Hardy-Weinberg equilibrium. The genotype and allele frequencies of the examined polymorphisms did not exhibit significant difference (P>0.05) between the groups. In the healthy and GDM pregnant women groups, the A-allele frequencies (95% CI) of FTO polymorphisms rs8050136 and rs9939609 were 39% (34-44%); 38% (33-43%) and 40% (35-45%); 41% (36-46%), respectively; and the T-allele frequencies of TCF7L2 polymorphisms rs12255372 and rs7903146 were 30% (26-35%), 32% (27-37%) and 29% (25-34%), 36% (31-41%), respectively. The examined polymorphisms were not associated with GDM in the Euro-Brazilian population studied. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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.

Lack of association between polymorphisms in genes MTHFR and MDR1 with risk of childhood acute lymphoblastic leukemia.

PubMed

Kreile, Madara; Rots, Dmitrijs; Piekuse, Linda; Cebura, Elizabete; Grutupa, Marika; Kovalova, Zhanna; Lace, Baiba

2014-01-01

Acute lymphoblastic leukemia (ALL) is a complex disease caused by interactions between hazardous exogenous or/and endogenous agents and many mild effect inherited susceptibility mutations. Some of them are known, but their functional roles still requireinvestigation. Age is a recognized risk factor; children with disease onset after the age of ten have worse prognosis, presumably also triggered by inherited factors. The MDR1 gene polymorphisms rs1045642, rs2032582 and MTHFR gene polymorphisms rs1801131 and rs1801133 were genotyped in 68 ALL patients in remission and 102 age and gender matched controls; parental DNA samples were also available for 42 probands. No case control association was found between analyzed polymorphisms and a risk of childhood ALL development. Linkage disequilibrium was not observed in a family-based association study either. Only marginal association was observed between genetic marker rs2032582A and later disease onset (p=0.04). Our data suggest that late age of ALL onset could be triggered by mild effect common alleles.

Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

PubMed

Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

2014-05-01

To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

Predictive Value of Gene Polymorphisms on Recurrence after the Withdrawal of Antithyroid Drugs in Patients with Graves’ Disease

PubMed Central

Liu, Jia; Fu, Jing; Duan, Yan; Wang, Guang

2017-01-01

Graves’ disease (GD) is one of the most common endocrine diseases. Antithyroid drugs (ATDs) treatment is frequently used as the first-choice therapy for GD patients in most countries due to the superiority in safety and tolerance. However, GD patients treated with ATD have a relatively high recurrence rate after drug withdrawal, which is a main limitation for ATD treatment. It is of great importance to identify some predictors of the higher recurrence risk for GD patients, which may facilitate an appropriate therapeutic approach for a given patient at the time of GD diagnosis. The genetic factor was widely believed to be an important pathogenesis for GD. Increasing studies were conducted to investigate the relationship between gene polymorphisms and the recurrence risk in GD patients. In this article, we updated the current literatures to highlight the predictive value of gene polymorphisms on recurrence risk in GD patients after ATD withdrawal. Some gene polymorphisms, such as CTLA4 rs231775, human leukocyte antigen polymorphisms (DRB1*03, DQA1*05, and DQB1*02) might be associated with the high recurrence risk in GD patients. Further prospective studies on patients of different ethnicities, especially studies with large sample sizes, and long-term follow-up, should be conducted to confirm the predictive roles of gene polymorphism. PMID:29085334

Val158Met polymorphism in the COMT gene is associated with hypersomnia and mental health-related quality of life in a Colombian sample.

PubMed

Jiménez, Karen M; Pereira-Morales, Angela J; Forero, Diego A

2017-03-22

The identification of genes that are risk factors for major depressive disorder remains a main task for global psychiatric research. The Catechol-O-methyltransferase (COMT) gene has been an important candidate risk factor for several psychiatric disorders. Previous studies have shown that a functional polymorphism (Val158Met) in this gene has an effect on several brain circuits and endophenotypes of psychiatric relevance. The aim of this study was to explore the association of a functional polymorphism in the COMT gene with psychological distress, sleep problems and health-related quality of life. Two hundred seventy young Colombian subjects (mean age: 21.3 years; range: 18-57 years) completed the Patient Health Questionnaire-9, the Perceived Stress Scale, the Oviedo Sleep Questionnaire and the 12-Item Short-Form Health Survey and were genotyped for the Val158Met polymorphism (rs4680) in the COMT gene. A linear regression analysis, adjusting for potential confounding factors, was carried out. Subjects that were Met carriers (Val/Met and Met/Met genotypes) showed higher scores for hypersomnia (p=0.001) and lower scores for mental health-related quality of life (p=0.007), these associations remained significant after correcting for multiple testing. These findings support the hypothesis of a broad effect of the Val158Met polymorphism in the COMT gene on several dimensions of behavior and neuropsychiatric symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

[Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus].

PubMed

Wang, Ming; Zhang, Li; Liu, Xinghui

2014-04-01

To explore the interactions between human leukocyte antigen (HLA) -DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus (GDM) pathogenesis. Pregnant women who had prenatal cares in Obstetric Department, West China Second Hospital of Sichuan University were recruited from January 1(st) to December 31(st) in 2011. A prospective cohort study was conducted in the women who had a glucose challenge test (GCT) or 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks. A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group. The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method in both groups. The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method. (1) There were 712 pregnant women with complete perinatal information during January 1(st) to December 31(st) , 2011, among whom 175 (24.6%) women were diagnosed with GDM. A logistic regression analysis showed that advanced maternal age (OR = 1.081, 95%CI: 1.027- 1.138), imbalanced diet (OR = 3.329, 95%CI: 2.167-5.116), high body mass index (BMI ≥ 24.0 kg/m(2)) before pregnancy (OR = 1.095, 95%CI:1.008-1.190), HBsAg carrier status (OR = 3.173, 95%CI: 1.387-7.260) and family history of diabetes mellitus (DM) (OR = 1.798, 95%CI: 1.063-3.041) were risk factors of GDM. (2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group, respectively. We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12, 16 was only detected in 5 cases (5/103, 4.9%) in control group, and the difference was significant between the two groups (P = 0.029). HLA-DRB1*11, 16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%, 4/104) and 5 cases (4.8%, 5/104) in GDM group respectively, but without significant

Polymorphic CA repeats in the IGF-I gene and breast cancer.

PubMed

Yu, H; Li, B D; Smith, M; Shi, R; Berkel, H J; Kato, I

2001-11-01

Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16-7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42-18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.

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

PubMed Central

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. PMID:24589462

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.

Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population.

PubMed

Han, Dong; Qiao, Zhengxue; Chen, Lu; Qiu, Xiaohui; Fang, Deyu; Yang, Xiuxian; Ma, Jingsong; Chen, Mingqi; Yang, Jiarun; Wang, Lin; Zhu, Xiongzhao; Zhang, Congpei; Yang, Yanjie; Pan, Hui

2017-08-01

Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence for polymorphism in the cytochrome P450 2D50 gene in horses.

PubMed

Corado, C R; McKemie, D S; Young, A; Knych, H K

2016-06-01

Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times. CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme that is highly polymorphic in humans leading to widely differing levels of metabolic activity. As CYP2D6 is highly polymorphic, in this study it was hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50 gene was cloned and sequenced; and full-length sequences were analyzed for single nucleotide polymorphisms (SNPs), deletions, or insertions. Pharmacokinetic data were collected from a subset of horses following the administration of a single oral dose of tramadol and probit analysis used to calculate metabolic ratios. Prior to drug administration, the ability of recombinant CYP2D50 to metabolize tramadol to O-desmethyltramadol was confirmed. Sequencing of CYP2D50 identified 126 exonic SNPs, with 31 of those appearing in multiple horses. Oral administration of tramadol to a subset of these horses revealed variable metabolic ratios (tramadol: O-desmethyltramadol) in individual horses and separation into three metabolic groups. While a limited number of horses of primarily a single breed were studied, the variability in tramadol metabolism to O-desmethyltramadol between horses and preliminary evidence of what appears to be poor, extensive, and ultra-rapid metabolizers supports further study of the potential for genetic polymorphisms in the CYP2D50 gene in horses. © 2015 John Wiley & Sons Ltd.

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.

Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder

PubMed Central

Gokcen, Cem; Kocak, Nadir; Pekgor, Ahmet

2011-01-01

Objective: The purpose of this study was to evaluate the relationship between 5,10- methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Attention Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. Study Design: MTHFR gene polymorphisms were assessed in 40 patients with ADHD and 30 healty controls. Two mutations in the MTHFR gene were investigated using polymerase chain reactions and restriction fragment length polymorphisms. Results: Although there were no statistically significant differences in genotype distributions of the C677T alleles between the ADHD and the control groups (p=0,678) but the genotypic pattern of the distributions of the A1298C alleles was different between the ADHD patients and the controls (p=0,033). Conclusions: Preliminary data imply a possible relationship between A1298C MTHFR polymorphisms and the ADHD. PMID:21897766

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

PubMed Central

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.

The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies havemore » found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.« less

Effect of interactions of polymorphisms in the Melanocortin-4 receptor gene with dietary factors on the risk of obesity and Type 2 diabetes: a systematic review.

PubMed

Koochakpoor, G; Hosseini-Esfahani, F; Daneshpour, M S; Hosseini, S A; Mirmiran, P

2016-08-01

To perform a systematic review of the effect of interaction between Melanocortin-4 receptor (MC4R) single nucleotide polymorphisms and diet on the development of obesity and Type 2 diabetes. Environmental factors, such as nutrient intakes or feeding behaviours, can modulate the association of polymorphism in the MC4R gene with obesity and Type 2 diabetes mellitus. A systematic literature search was conducted in the PubMed, Scopus and Google Scholar databases, with a combination of the following keywords: Diet*, nutr*, melanocortin receptor, melanocortin 4 receptor and MC4R. To assess the quality of observational studies, we used a 12-item quality checklist, derived from the STREGA statement. A total of 14 articles were selected based on the inclusion and exclusion criteria. Consumption of highly salty foods and adherence to a Mediterranean dietary pattern can modulate the association between MC4R polymorphisms and the risk of obesity or Type 2 diabetes. Despite the highly contradictory results of intervention studies, after short-term lifestyle interventions, children with variant alleles of MC4R single nucleotide polymorphisms can lose more body weight, compared with non-carriers, although they may have difficulty in maintaining this weight loss in the long-term. To interpret the results of studies on adults, we need further studies. The interaction between MC4R genes with dietary factors plays a significant role in the development of obesity or Type 2 diabetes phenotypes. Early detection of MC4R risk alleles in individuals and modification of their diet based on these results could be an efficient strategy to prevent obesity or diabetes in these subgroups. © 2015 Diabetes UK.

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

PubMed

Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

2014-01-01

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

The first report of prion-related protein gene (PRNT) polymorphisms in goat.

PubMed

Kim, Yong-Chan; Jeong, Byung-Hoon

2017-06-01

Prion protein is encoded by the prion protein gene (PRNP). Polymorphisms of several members of the prion gene family have shown association with prion diseases in several species. Recent studies on a novel member of the prion gene family in rams have shown that prion-related protein gene (PRNT) has a linkage with codon 26 of prion-like protein (PRND). In a previous study, codon 26 polymorphism of PRND has shown connection with PRNP haplotype which is strongly associated with scrapie vulnerability. In addition, the genotype of a single nucleotide polymorphism (SNP) at codon 26 of PRND is related to fertilisation capacity. These findings necessitate studies on the SNP of PRNT gene which is connected with PRND. In goat, several polymorphism studies have been performed for PRNP, PRND, and shadow of prion protein gene (SPRN). However, polymorphism on PRNT has not been reported. Hence, the objective of this study was to determine the genotype and allelic distribution of SNPs of PRNT in 238 Korean native goats and compare PRNT DNA sequences between Korean native goats and several ruminant species. A total of five SNPs, including PRNT c.-114G > T, PRNT c.-58A > G in the upstream of PRNT gene, PRNT c.71C > T (p.Ala24Val) and PRNT c.102G > A in the open reading frame (ORF) and c.321C > T in the downstream of PRNT gene, were found in this study. All five SNPs of caprine PRNT gene in Korean native goat are in complete linkage disequilibrium (LD) with a D' value of 1.0. Interestingly, comparative sequence analysis of the PRNT gene revealed five mismatches between DNA sequences of Korean native goats and those of goats deposited in the GenBank. Korean native black goats also showed 5 mismatches in PRNT ORF with cattle. To the best of our knowledge, this is the first genetic research of the PRNT gene in goat.

[Alzheimer's disease and methylenetetrahydrofolate reductase gene polymorphisms: a potential nutrigenomic approach for Mexico].

PubMed

Castillo-Quan, Jorge I; Pérez-Osorio, Julia M

2009-01-01

The establishment of medical genomics in Mexico offers the possibility to study in a more comprehensive manner the etiological factors of different diseases, providing a global view of the interaction between the genome and the environment. Nutrition is recognized as a significant determinant in several diseases, yet its interaction with polymorphisms, and in general with the genome, has not been properly addressed Mexico has a high prevalence of polymorphisms of the methylenetetrahydrofolate reductase gene, and in both clinical and basic studies this has been associated with an increased susceptibility of developing Alzheimer's disease. We propose a potential nutrigenomic approach for the study of Alzheimer disease in Mexico.

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

PubMed

Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p < 0.05). Analysis of ACE gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat.

PubMed

Brevik, Asgeir; Joshi, Amit D; Corral, Román; Onland-Moret, N Charlotte; Siegmund, Kimberly D; Le Marchand, Loïc; Baron, John A; Martinez, Maria Elena; Haile, Robert W; Ahnen, Dennis J; Sandler, Robert S; Lance, Peter; Stern, Mariana C

2010-12-01

A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Using a family-based study, we investigated the role of polymorphisms in 4 BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; and XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between diets high in red meat or poultry and CRC risk. We tested for gene-environment interactions using case-only analyses (n = 577) and compared statistically significant results with those obtained using case-unaffected sibling comparisons (n = 307 sibships). Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared with carriers of the Gln/Gln genotype (odds ratio (OR) = 0.15, 95% CI = 0.03-0.69, P = 0.015). The association between higher red meat intake (>3 servings per week) and CRC was modified by the PARP Val762Ala single-nucleotide polymorphisms (SNP; case-only interaction P = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction P = 0.0009). We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a diet high in red meat. ©2010 AACR.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

PubMed

Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

2017-01-01

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR , FABP2 , FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE , FABP2 , FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

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.

Estimation of the relationship between the polymorphisms of selected genes: ACE, AGTR1, TGFβ1 and GNB3 with the occurrence of primary vesicoureteral reflux.

PubMed

Życzkowski, Marcin; Żywiec, Joanna; Nowakowski, Krzysztof; Paradysz, Andrzej; Grzeszczak, Władyslaw; Gumprecht, Janusz

2017-03-01

Etiopathogenesis of VUR is composite and not fully understood. Many data indicate the importance of genetic predisposition. The aim of this study was to establish the relationship of selected polymorphisms: 14094 polymorphism of the ACE, polymorphism rs1800469 of TGFβ-1, rs5443 gene polymorphism of the GNB3 and receptor gene polymorphism rs5186 type 1 AGTR1 with the occurrence of the primary vesicoureteral reflux. The study included 190 children: 90 with the primary VUR confirmed with the voiding cystourethrogram and excluded secondary VUR and a control group of 100 children without a history of the diseases of the genitourinary tract. The study was planned in the scheme: "tested case versus control." Genomic DNA was isolated from the leukocytes of peripheral blood samples. The results were statistically analyzed in the Statistica 10 using χ 2 test and analysis of the variance Anova. Any of the four studied polymorphisms showed no difference in the distribution of genotypes between patients with primary vesicoureteral reflux and the control group. In patients with VUR and TT genotype polymorphism rs5443 GNB3 gene, the glomerular filtration rate was significantly higher than in patients with genotype CC or CT. (1) No relationship was found between the studied polymorphisms (14094 ACE gene, rs1800469 gene TGFβ1, GNB3 gene rs5443, rs5186 AGTR1 gene) and the occurrence of primary vesicoureteral reflux. (2) TT genotype polymorphism rs5443 GNB3 gene may be a protective factor for the improved renal function in patients with primary vesicoureteral reflux in patients with genotype CC or CT.

IL-10 and IL-12B gene polymorphisms in a multiethnic Malaysian population.

PubMed

Sam, S S; Teoh, B T; AbuBakar, S

2015-04-13

Inheritance of polymorphisms in the interleukin (IL)-10 promoter and IL-12B genes, which influence cytokine production and activities, may define the balance in T helper response in infection and autoimmune diseases. In the present study, we investigated the distribution of the IL-10 promoter and IL-12B gene polymorphisms in a multiethnic Malaysian population. Overall, our findings suggest that the IL-12B and IL-10 -592 genotypes were distributed homogenously across all major ethnic groups, including Malays, Chinese, and Indians, except for polymorphisms at IL-10 -1082. At this gene locus, the ethnic Chinese showed a significantly lower allele frequency of -1082G (2.1%) compared to the Malay (12.2%) and Indian (15.3%) populations. Results for the IL-12B and IL-10 gene polymorphisms were consistent with those reported for the Asian population, but markedly different from those of the African and Caucasian populations. Our findings suggest that there are specific genetic variations between different ethnic groups, which should be examined in all gene population-based association studies.

Cytokine gene polymorphisms in Italian preterm infants: association between interleukin-10 -1082 G/A polymorphism and respiratory distress syndrome.

PubMed

Capasso, Mario; Avvisati, Rosa Anna; Piscopo, Carmelo; Laforgia, Nicola; Raimondi, Francesco; de Angelis, Filomena; Iolascon, Achille

2007-03-01

In this study, we determined the genotype frequencies of polymorphisms of cytokine genes and investigated their association with the risk of respiratory distress syndrome (RDS) in preterm infants. Genetic polymorphisms in the cytokines interleukin (IL)-10, IL-8, and tumor necrosis factor (TNF) alpha, were studied in 342 white Italian newborns (112 without RDS, 66 prematurely born with RDS, and 164 infants born at term who were included as healthy controls). The polymorphisms were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). The IL-10 mRNA levels were analyzed according to genotype by quantitative real-time PCR (QRT-PCR) in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) of 42 full-term healthy infants. Logistic regression analysis demonstrated the risk of RDS to be significantly lower in preterm infants with an IL-10 -1082 GG/GA genotype than in those with an AA genotype [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.24-0.95, p = 0.03]. QRT-PCR analyses showed that the IL-10 mRNA levels were significantly higher in 27 IL-10 -1082 GG/GA carriers compared with 15 IL-10 -1082 AA carriers (p = 0.03). We conclude that the IL-10 -1082 GG/GA polymorphism may have a role in RDS development in premature infants.

Polymorphism of BMP4 gene in Indian goat breeds differing in prolificacy.

PubMed

Sharma, Rekha; Ahlawat, Sonika; Maitra, A; Roy, Manoranjan; Mandakmale, S; Tantia, M S

2013-12-10

Bone morphogenetic proteins (BMPs) are members of the TGF-β (transforming growth factor-beta) superfamily, of which BMP4 is the most important due to its crucial role in follicular growth and differentiation, cumulus expansion and ovulation. Reproduction is a crucial trait in goat breeding and based on the important role of BMP4 gene in reproduction it was considered as a possible candidate gene for the prolificacy of goats. The objective of the present study was to detect polymorphism in intronic, exonic and 3' un-translated regions of BMP4 gene in Indian goats. Nine different goat breeds (Barbari, Beetal, Black Bengal, Malabari, Jakhrana (Twinning>40%), Osmanabadi, Sangamneri (Twinning 20-30%), Sirohi and Ganjam (Twinning<10%)) differing in prolificacy and geographic distribution were employed for polymorphism scanning. Cattle sequence (AC_000167.1) was used to design primers for the amplification of a targeted region followed by direct DNA sequencing to identify the genetic variations. Single nucleotide polymorphisms (SNPs) were not detected in exon 3, the intronic region and the 3' flanking region. A SNP (G1534A) was identified in exon 2. It was a non-synonymous mutation resulting in an arginine to lysine change in a corresponding protein sequence. G to A transition at the 1534 locus revealed two genotypes GG and GA in the nine investigated goat breeds. The GG genotype was predominant with a genotype frequency of 0.98. The GA genotype was present in the Black Bengal as well as Jakhrana breed with a genotype frequency of 0.02. A microsatellite was identified in the 3' flanking region, only 20 nucleotides downstream from the termination site of the coding region, as a short sequence with more than nineteen continuous and repeated CA dinucleotides. Since the gene is highly evolutionarily conserved, identification of a non-synonymous SNP (G1534A) in the coding region gains further importance. To our knowledge, this is the first report of a mutation in the coding

Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies.

PubMed

Johns, N; Tan, B H; MacMillan, M; Solheim, T S; Ross, J A; Baracos, V E; Damaraju, S; Fearon, K C H

2014-12-01

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

CCDC22 gene polymorphism is associated with advanced stages of endometriosis in a sample of Brazilian women.

PubMed

de Oliveira Francisco, Daniela; de Paula Andres, Marina; Gueuvoghlanian-Silva, Bárbara Yasmim; Podgaec, Sergio; Fridman, Cintia

2017-07-01

Based on the assumption that genetic factors are involved in the etiology of endometriosis, this study aimed to investigate the possibility of rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), and rs2294021 (CCDC22 gene) polymorphisms being associated with the occurrence of this disease in a sample of Brazilian women. We conducted a case-control study with 100 women with histological confirmation of endometriosis (endometriosis group) and 100 women submitted to laparoscopy for benign disorders, in which the absence of endometriosis was confirmed (control group). All samples were genotyped by real-time PCR technique for rs498679, rs1799964, rs3024496, and rs2294021 polymorphisms. No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), neither when comparing endometriosis subgroups (I-II versus III-IV). On the other hand, significant difference between stages I-II and III-IV of the disease was found in genotypic and allelic frequencies for the rs2294021 (CCDC22 gene) SNP (p = 0.048 and p = 0.017, respectively). Our results suggest that the rs2294021 (CCDC22 gene) polymorphism could be associated with increased susceptibility to endometriosis in Brazilian women when the allele C is present. In order to clarify this result, further studies should be conducted on a larger population.

Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease.

PubMed

Mlak, Radosław; Homa-Mlak, Iwona; Powrózek, Tomasz; Mackiewicz, Barbara; Michnar, Marek; Krawczyk, Paweł; Dziedzic, Marcin; Rubinsztajn, Renata; Chazan, Ryszarda; Milanowski, Janusz; Małecka-Massalska, Teresa

2016-04-01

Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought.

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

PubMed Central

Alvelos, Inês; Mendes, Adélia; Santos, Liliana R.; Machado, José Carlos; Melo, Miguel; Esteves, César; Neves, Celestino; Sobrinho-Simões, Manuel; Soares, Paula

2014-01-01

Background Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD. Methods Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays. Results A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37–2.43, p-value = 4.4×10−5) and log-additive (OR = 1.64, CI = 1.28–2.10, p-value = 8.2×10−5) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06–1.54, p-value = 8.9×10−3). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19–2.87, p-value = 7.0×10−3) and log-additive (OR = 1.69, CI = 1.17–2.44, p-value = 6.6×10−3) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59). Conclusions This study reports significant associations of genetic variants in TNFA and

Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis

PubMed Central

Marinković, Natalija; Pašalić, Daria; Potočki, Slavica

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are among the most prevalent environmental pollutants and result from the incomplete combustion of hydrocarbons (coal and gasoline, fossil fuel combustion, byproducts of industrial processing, natural emission, cigarette smoking, etc.). The first phase of xenobiotic biotransformation in the PAH metabolism includes activities of cytochrome P450 from the CYP1 family and microsomal epoxide hydrolase. The products of this biotransformation are reactive oxygen species that are transformed in the second phase through the formation of conjugates with glutathione, glucuronate or sulphates. PAH exposure may lead to PAH-DNA adduct formation or induce an inflammatory atherosclerotic plaque phenotype. Several genetic polymorphisms of genes encoded for enzymes involved in PAH biotransformation have been proven to lead to the development of diseases. Enzyme CYP P450 1A1, which is encoded by the CYP1A1 gene, is vital in the monooxygenation of lipofilic substrates, while GSTM1 and GSTT1 are the most abundant isophorms that conjugate and neutralize oxygen products. Some single nucleotide polymorphisms of the CYP1A1 gene as well as the deletion polymorphisms of GSTT1 and GSTM1 may alter the final specific cellular inflammatory respond. Occupational exposure or conditions from the living environment can contribute to the production of PAH metabolites with adverse effects on human health. The aim of this study was to obtain data on biotransformation and atherosclerosis, as well as data on the gene polymorphisms involved in biotransformation, in order to better study gene expression and further elucidate the interaction between genes and the environment. PMID:24266295

Insulin-like growth factor I gene polymorphism associated with growth and carcass traits in Thai synthetic chickens.

PubMed

Promwatee, N; Laopaiboon, B; Vongpralub, T; Phasuk, Y; Kunhareang, S; Boonkum, W; Duangjinda, M

2013-03-15

Four Thai synthetic chicken lines (Kaen Thong, Khai Mook Esarn, Soi Nin, and Soi Pet) originated from Thai native and exotic commercial chickens were evaluated for their growth and carcass traits with the purpose of developing a Thai broiler breeding program. Insulin-like growth factor I (IGF-I) gene is known to play an important role in growth, proliferation and differentiation. Consequently, we investigated the possibility of using the IGF-I gene for marker-assisted selection in Thai synthetic chickens. We looked for variations in the IGF-I gene and studied their association with growth and carcass traits; 1046 chickens were genotyped using PCR-RFLP methods. A general linear model was used to analyze associations of the IGF-I polymorphism with growth and carcass traits. Kaen Thong, Khai Mook Esarn, and Soi Nin chickens were found to carry similar frequencies of alleles A and C (0.40-0.60), while Soi Pet chickens had high frequencies of allele C (0.75). The IGF-I gene was significantly associated with some growth traits (body weight at hatching, and at 4, 8, 12, and 14 weeks of age; average daily gain during 0-12 and 0-14 weeks of age) in all synthetic chickens. Carcass traits (the percentage of dressing and pectoralis major) were significantly different only in Khai Mook Esarn chickens. We conclude that IGF-I can be used as a marker gene for the selection of growth and carcass traits of synthetic chickens in a marker-assisted selection program.

Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

PubMed

Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

2016-01-01

In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

Genetic polymorphisms in the formaldehyde dehydrogenase gene and their biological significance.

PubMed

Just, Walter; Zeller, Jasmin; Riegert, Clarissa; Speit, Günter

2011-11-30

The GSH-dependent formaldehyde dehydrogenase (FDH) is the most important enzyme for the metabolic inactivation of formaldehyde. We studied three polymorphisms of this gene with the intention to elucidate their relevance for inter-individual differences in the protection against the (geno-)toxicity of FA. The first polymorphism (rs11568816) was investigated using real-time PCR and restriction fragment analysis in 150 subjects. However, we did not find the polymorphic sequence in any of the subjects. We studied a second polymorphism (rs17028487), representing a base exchange (c.*114A>G) in exon 9 of the FDH gene. We analyzed 70 subjects with the SNaPshot Primer Extension method and subsequent analysis in a ABI PRISM 3100, but no variant allele was identified. A third polymorphism, rs13832 in exon 9 (c.*493G>T), was studied in a group of 105 subjects by the SNaPshot Primer Extension method. 43 of the subjects were heterozygous for the polymorphism (G/T), 46 homozygous for the T allele, and 16 were homozygous for the G-allele. Real-time RT-PCR measurements of FDH mRNA did not indicate a significant difference in transcript levels between the heterozygous and the homozygous groups. The in vitro comet assay after FA exposure of blood samples obtained from 5 homozygous GG and 3 homozygous TT subjects did not lead to a significant difference between these two groups. Altogether, our study did not identify biologically relevant polymorphisms in transcribed regions of the FDH gene, which may lead to inter-individual differences in the metabolic inactivation of FA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease.

PubMed

Masud, Rizwan; Qureshi, Irfan Zia

2011-09-01

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

An Association Study of the SLC19A1 Gene Polymorphisms/Haplotypes with Idiopathic Recurrent Pregnancy Loss in an Iranian Population.

PubMed

Mohtaram, Shirin; Sheikhha, Mohammad Hasan; Honarvar, Negar; Sazegari, Ali; Maraghechi, Neda; Feizollahi, Zahra; Ghasemi, Nasrin

2016-05-01

The genetics of folate metabolism is one of the most significant mechanisms influencing fetal growth and may underlie some cases of unexplained recurrent miscarriage. Reduced folate carrier 1, encoded by the SLC19A1 gene, is a transporter of folate. Folate deficiency and elevated levels of homocysteine could be disadvantageous for the female reproductive system health. Thus, the balance between homocysteine and folate status can be used to measure the risk of recurrent pregnancy loss. The purpose of this study was to determine the association between -43T>C, 80G>A, and 696C>T polymorphisms of the SLC19A1 gene in 147 women who had unexplained recurrent miscarriage in comparison with 150 healthy women. Amplification refractory mutation system-polymerase chain reaction was used to genotype the molecular polymorphisms of this gene. The results indicated that the -43T>C single nucleotide of the SLC19A1 gene was significantly associated with a risk of recurrent miscarriage in Iranian women (p < 0.05). No significant association was observed for the other two polymorphisms. The haplotype frequency distribution of -43C/80G/696C, -;43C/80G/696T, -43C/80G, and 80G/696T was significantly different in patients than controls, which may represent a novel risk factor for idiopathic recurrent pregnancy loss. Polymorphisms and haplotypes of the SLC19A1 gene can be considered risk factors for idiopathic recurrent pregnancy loss.

Frequency of polymorphism -262 c/t in catalase gene and oxidative damage in Slovak children with bronchial asthma.

PubMed

Babusikova, Eva; Jesenak, Milos; Evinova, Andrea; Banovcin, Peter; Dobrota, Dusan

2013-12-01

Bronchial asthma is a complex disease in which genetic factors, environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression. If antioxidant mechanisms fail, reactive oxygen species damage the biomolecules followed by progression of the disease. Catalase is one of the most important endogenous enzymatic antioxidants. In the present study, we examined the hypothesis that increased oxidative damage and polymorphism in the CAT gene (-262 promoter region, C/T) are associated with childhood bronchial asthma. Genotyping of the polymorphisms in the CAT gene in healthy (249) and asthmatic children (248) was performed using polymerase chain reaction-restriction fragment length polymorphism. Markers of oxidative damage: content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children. The TT genotype of catalase was more frequent among the asthmatic patients (22.6%) than in healthy children (4.8%) (odds ratio=5.63; 95% confidence interval=2.93-10.81, P<.001). The amount of sulfhydryl groups decreased significantly and conversely, the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene. These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children. Genetic variation of enzymatic antioxidants may modulate disease risk. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population.

PubMed

Atilla, Mahmut Huntürk; Özdaş, Sibel; Özdaş, Talih; Baştimur, Sibel; Muz, Sami Engin; Öz, Işılay; Kurt, Kenan; İzbirak, Afife; Babademez, Mehmet Ali; Vatandaş, Nilgün

2017-08-01

Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p=0.012, p=0.009, p=0.013, and p=0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5' to 3'; p=0.0001). Polymorfism-Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p<0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and adenoid hypertrophy with allergies (p=0.003 and p=0.0007, respectively). Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy

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.

Transcription Factor Binding Site Polymorphism in the Motilin Gene Associated with Left-Sided Displacement of the Abomasum in German Holstein Cattle

PubMed Central

Mömke, Stefanie; Sickinger, Marlene; Rehage, Jürgen; Doll, Klaus; Distl, Ottmar

2012-01-01

Left-sided displacement of the abomasum (LDA) is a common disease in many dairy cattle breeds. A genome-wide screen for QTL for LDA in German Holstein (GH) cows indicated motilin (MLN) as a candidate gene on bovine chromosome 23. Genomic DNA sequence analysis of MLN revealed a total of 32 polymorphisms. All informative polymorphisms used for association analyses in a random sample of 1,136 GH cows confirmed MLN as a candidate for LDA. A single nucleotide polymorphism (FN298674:g.90T>C) located within the first non-coding exon of bovine MLN affects a NKX2-5 transcription factor binding site and showed significant associations (ORallele = 0.64; −log10Pallele = 6.8, −log10Pgenotype = 7.0) with LDA. An expression study gave evidence of a significantly decreased MLN expression in cows carrying the mutant allele (C). In individuals heterozygous or homozygous for the mutation, MLN expression was decreased by 89% relative to the wildtype. FN298674:g.90T>C may therefore play a role in bovine LDA via the motility of the abomasum. This MLN SNP appears useful to reduce the incidence of LDA in German Holstein cattle and provides a first step towards a deeper understanding of the genetics of LDA. PMID:22536407

Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea.

PubMed

Özdaş, Sibel; Özdaş, Talih; Acar, Mustafa; Erbek, Selim S; Köseoğlu, Sabri; Göktürk, Gökhan; Izbirak, Afife

2016-05-01

Interleukin-10 (IL) is an anti-inflammatory cytokine that regulates normal sleep patterns, and recent studies have reported that it is a potential useful biomarker to identify presence and severity of sleep apnea syndrome (OSAS). Promoter polymorphisms of IL-10 gene have been associated with altered expression levels, which contributes to OSAS. The aim of this study was to determine the prevalence of -1082 G/A, -819 C/T, and -592 C/A promoter polymorphisms of IL-10 gene in individuals with OSAS and controls. An open-label study was performed in the Otorhinolaryngology and Sleep Disorders Outpatient Clinics. One hundred four cases with OSAS were included as the study group, and 78 individuals without OSAS were included as the controls. DNAs were extracted from peripheral blood leukocytes, and the sites that encompassed those polymorphisms were identified by DNA sequencing analyses. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. The prevalence of OSAS was higher in males in the study group when compared to controls (P = 0.0003). The IL-10-1082 G/A, -819 C/T, and -592 C/A SNPs, and their minor alleles were associated with a significantly increased risk for OSAS compared to the controls (P ˂ 0.05 for all). Furthermore, ATA haplotype frequency was significantly higher in the study group compared to the control group, but the GCC haplotype frequency was lower (P = 0.0001 and P = 0.0001). As indicated in MDR analysis, combinations of IL-10 gene were associated with OSAS in single-, double-, and triple-locus analyses. The prevalences of the IL-10 gene promoter polymorphisms were different in OSAS patients and the controls in Turkish population. IL-10 gene polymorphisms may lead to altered inflammatory cascade, which might contribute to OSAS. Further studies on larger cohorts are needed to validate our findings.

Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis.

PubMed

Atar, Arda; Gedikbasi, Asuman; Sonmezay, Erkan; Kiraz, Zeynep Kusku; Abbasoglu, Semra; Tasci, Ali Ihsan; Tugcu, Volkan

2016-01-01

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

Analysis of the Functional Polymorphism in the Cytochrome P450 CYP2C8 Gene rs11572080 with Regard to Colorectal Cancer Risk

PubMed Central

Ladero, José M.; Agúndez, José A. G.; Martínez, Carmen; Amo, Gemma; Ayuso, Pedro; García-Martín, Elena

2012-01-01

In addition to the known effects on drug metabolism and response, functional polymorphisms of genes coding for xenobiotic-metabolizing enzymes (XME) play a role in cancer. Genes coding for XME act as low-penetrance genes and confer modest but consistent and significant risks for a variety of cancers related to the interaction of environmental and genetic factors. Consistent evidence supports a role for polymorphisms of the cytochrome P450 CYP2C9 gene as a protecting factor for colorectal cancer susceptibility. It has been shown that CYP2C8 and CYP2C9 overlap in substrate specificity. Because CYP2C8 has the common functional polymorphisms rs11572080 and rs10509681 (CYP2C8*3), it could be speculated that part of the findings attributed to CYP2C9 polymorphisms may actually be related to the presence of polymorphisms in the CYP2C8 gene. Nevertheless, little attention has been paid to the role of the CYP2C8 polymorphism in colorectal cancer. We analyzed the influence of the CYP2C8*3 allele in the risk of developing colorectal cancer in genomic DNA from 153 individuals suffering colorectal cancer and from 298 age- and gender-matched control subjects. Our findings do not support any effect of the CYP2C8*3 allele (OR for carriers of functional CYP2C8 alleles = 0.50 (95% CI = 0.16–1.59; p = 0.233). The absence of a relative risk related to CYP2C8*3 did not vary depending on the tumor site. We conclude that the risk of developing colorectal cancer does not seem to be related to the commonest functional genetic variation in the CYP2C8 gene. PMID:23420707

Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection.

PubMed

Coelho, Verônica Porto Carreiro de Vasconcellos; Ioschpe, Rafael; Caldas, Cristina; Spadafora-Ferreira, Monica; Fonseca, João Americo; Cardoso, Maria Regina Alves; Palacios, Selma Aliotti; Kalil, Jorge; Goldberg, Anna Carla

2011-03-01

To assess the long-term impact (minimum of 3 years follow-up) of polymorphisms in cytokine genes in donor:recipient pairs on the results of the transplant. We compared genetic cytokine polymorphisms and the primary factors of risk for the development of chronic rejection in paired groups of renal transplant patients with and without chronic allograft nephropathy [CAN]. Multivariate analysis indicated that the presence of the high-production TT genotype (codon 10) of the transforming growth factor beta-1 (TGFB1) was protective in receptors (p=0.017), contrasting with the increased risk when present in donor samples (p=0.049). On the other hand, in the case of the gamma interferon studied, the greater frequency of the high production allele was protective in the analysis of the donor group (p=0.013), increasing the risk of chronic nephropathy of the allograft when present in the recipients (p=0.036). Our results highlight the importance of TGFB1 genotyping in donors, and indicate that polymorphisms in the gene of this cytokine in donor cells might contribute to the development of chronic allograft nephropathy.

[Correlation analysis between single nucleotide polymorphism of FGF5 gene and wool yield in rabbits].

PubMed

Li, Chun-Xiao; Jiang, Mei-Shan; Chen, Shi-Yi; Lai, Song-Jia

2008-07-01

Single nucleotide polymorphism (SNP) in exon 1 and 3 of fibroblast growth factor (FGF5) gene was studied by DNA sequencing in Yingjing angora rabbit, Tianfu black rabbit and California rabbit. A frameshift mutation (TCT insert) at base position 217 (site A) of exon 1 and a T/C missense mutation at base position 59 (site B) of exon 3 were found in Yingjing angora rabbit with a high frequency; a T/C same-sense mutation at base position 3 (site C) of exon 3 was found with similar frequency in three rabbit breeds. Least square analysis showed that different genotypes had no significant association with wool yield in site A, and had high significant association with wool yield in site B (P<0.01) and significant association with wool yield in site C (P<0.05). It was concluded from the results that FGF5 gene could be the potential major gene affecting wool yield or link with the major gene, and polymorphic loci B and C may be used as molecular markers for im-proving wool yield in angora rabbits.

Cloning, tissue expression and polymorphisms of chicken Krüppel-like factor 7 gene.

PubMed

Zhang, Zhi-Wei; Wang, Zhi-Peng; Zhang, Kun; Wang, Ning; Li, Hui

2013-07-01

Krüppel-like factor 7 (KLF7) has been extensively studied in mammalian species, but its role in birds is still unclear. In the current study, cloning and sequencing showed that the full-length coding region of chicken KLF7 (Gallus gallus KLF7, gKLF7) was 891 bp long, encoding 296 amino acids. In addition, real-time RT-PCR analysis showed that gKLF7 was broadly expressed in all 15 chicken tissues selected, and its expression was significantly different in spleen, proventriculus, abdominal fat, brain, leg muscle, gizzard and heart between fat and lean broilers at 7 weeks of age. Additionally, one novel single nucleotide polymorphism (SNP), XM_426569.3: c. A141G, was identified in the second exon of gKLF7. Association analysis showed that this locus was significantly associated with fatness traits in Arbor Acres broiler random population and the eighth generation of Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) population (P < 0.05). These results suggest that gKLF7 might be a candidate gene for chicken fatness traits. © 2013 Japanese Society of Animal Science.

Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans.

PubMed

Rand, D M; Kann, L M

1996-07-01

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.

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.

PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis

PubMed Central

Tay, G K; Hui, J; Gaudieri, S; Schmitt-Egenolf, M; Martinez, O P; Leelayuwat, C; Williamson, J F; Eiermann, T H; Dawkins, R L

2000-01-01

The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis. PMID:10691930

Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population.

PubMed

Bigdeli, Razieh; Younesi, Mohammad Reza; Panahnejad, Erfan; Asgary, Vahid; Heidarzadeh, Samaneh; Mazaheri, Hoda; Aligoudarzi, Samira Louni

2018-04-15

Miscarriage is the most common complication in pregnancy. Considering the importance of the problem thrombophilia in pregnant women and its association with recurrent pregnancy loss (RPL), analysis of polymorphisms of genes involved in thrombophilia can be useful. We investigated the frequency and association between ten polymorphisms of seven thrombophilia genes and RPL in an Iranian population. This case-control study was conducted on 200 women with recurrent pregnancy loss and also on 200 women with at least one successful pregnancy as the control group. Using PCR-RFLP, DNA from samples were analyzed for carrying A5279G, A4070G, and FV Leiden of factor V; FXIII (Val34Leu); FII (A20210G); BF (-455 G⁄A); ITGB3 (1565T⁄C); 677C/T and 1298A/C of MTHFR; and PAI-1 (-675 I/D, 5G/4G) polymorphisms. The BF(-455 G⁄A), MTHFR (677 C⁄T, 1298A⁄ C), PAI-1 (-675 I/D,4G⁄ 5G), FV Leiden, FV (A5279G), FXIII (Val34Leu) polymorphisms, which had shown positive relation, and ITGB3 1565T⁄C were the polymorphisms with negative relation to RPL. But in this study it is indicated that there is no significant association between FII (A20210G) and FV (A4070G) polymorphism and RPL. All the data acquired from the RPL patients in this experiment illustrate the importance of screening thrombophilia. Nevertheless, more studies on large-scale populations may be needed to identify novel genetic variants. ASRM: American Society of Reproductive Medicine; HHCY: hyperhomocysteinemia; MTHFR: methylenetetrahydrofolate reductase; PCR: polymerase chain reaction; PAGE: poly-acrylamide gel electrophoresis; RPL: recurrent pregnancy loss.

Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

ERIC Educational Resources Information Center

Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

2010-01-01

The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine.

PubMed

Ovsyannikova, Inna G; Jacobson, Robert M; Dhiman, Neelam; Vierkant, Robert A; Pankratz, V Shane; Poland, Gregory A

2008-05-01

Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine. To identify genetic factors that might contribute to variations in mumps vaccine-induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12-18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination. These data suggest the important role of HLA and immunoregulatory cytokine receptor

Molecular basis of length polymorphism in the human zeta-globin gene complex.

PubMed Central

Goodbourn, S E; Higgs, D R; Clegg, J B; Weatherall, D J

1983-01-01

The length polymorphism between the human zeta-globin gene and its pseudogene is caused by an allele-specific variation in the copy number of a tandemly repeating 36-base-pair sequence. This sequence is related to a tandemly repeated 14-base-pair sequence in the 5' flanking region of the human insulin gene, which is known to cause length polymorphism, and to a repetitive sequence in intervening sequence (IVS) 1 of the pseudo-zeta-globin gene. Evidence is presented that the latter is also of variable length, probably because of differences in the copy number of the tandem repeat. The homology between the three length polymorphisms may be an indication of the presence of a more widespread group of related sequences in the human genome, which might be useful for generalized linkage studies. PMID:6308667

Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

PubMed

Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

2016-10-01

Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders.

PubMed

Kindler, Jochen; Bailer, Ursula; de Zwaan, Martina; Fuchs, Karoline; Leisch, Friedrich; Grün, Bettina; Strnad, Alexandra; Stojanovic, Mirjana; Windisch, Julia; Lennkh-Wolfsberg, Claudia; El-Giamal, Nadja; Sieghart, Werner; Kasper, Siegfried; Aschauer, Harald

2011-06-01

Genetic factors likely contribute to the biological vulnerability of eating disorders. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism.

PubMed

Cieślińska, Anna; Kostyra, Elżbieta; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Fiedorowicz, Ewa; Teodorowicz, Małgorzata; Savelkoul, Huub F J

2017-09-09

Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D₃ has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene. Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated. We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D₃ concentration in serum of ASD children. Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D₃ metabolism, while vitamin D₃ levels were not significantly different between ASD and non-ASD children.

Initial evidence that polymorphisms in neurotransmitter-regulating genes contribute to being born small for gestational age

PubMed Central

Morgan, Angharad R.; Thompson, John M.D.; Waldie, Karen E.; Cornforth, Christine M.; Turic, Darko; Sonuga-Barke, Edmund J.S.; Lam, Wen-Jiun; Ferguson, Lynnette R.; Mitchell, Edwin A.

2012-01-01

Being born small for gestational age (SGA) is a putative risk factor for the development of later cognitive and psychiatric health problems. While the inter-uterine environment has been shown to play an important role in predicting birth weight, little is known about the genetic factors that might be important. Here we test the hypothesis that neurotransmitter-regulating genes implicated in psychiatric disorders previously shown to be associated with SGA (such as attention-deficit hyperactivity disorder) are themselves predictive of SGA. DNA was collected from 227 SGA and 319 appropriate for gestational age children taking part in the Auckland Birthweight Collaborative Study. Candidate single nucleotide polymorphisms in genes regulating activity within dopamine, serotonin, glutamate and gamma-aminobutyric acid pathways were genotyped. Multiple regression analysis, controlling for potentially confounding factors, supported nominally significant associations between SGA and single nucleotide polymorphisms in COMT, HTR2A, SLC1A1 and SLC6A1. This is the first evidence that genes implicated in psychiatric disorders previously linked to SGA status themselves predict SGA. This highlights the possibility that the link between SGA and psychiatric disorders such as attention-deficit hyperactivity disorder may in part be genetically determined – that SGA marks pre-existing genetic risk for later problems. PMID:27625810

Microarray study of single nucleotide polymorphisms and expression of ATP-binding cassette genes in breast tumors

NASA Astrophysics Data System (ADS)

Tsyganov, M. M.; Ibragimova, M. K.; Karabut, I. V.; Freydin, M. B.; Choinzonov, E. L.; Litvyakov, N. V.

2015-11-01

Our previous research establishes that changes of expression of the ATP-binding cassette genes family is connected with the neoadjuvant chemotherapy effect. However, the mechanism of regulation of resistance gene expression remains unclear. As many researchers believe, single nucleotide polymorphisms can be involved in this process. Thereupon, microarray analysis is used to study polymorphisms in ATP-binding cassette genes. It is thus found that MDR gene expression is connected with 5 polymorphisms, i.e. rs241432, rs241429, rs241430, rs3784867, rs59409230, which participate in the regulation of expression of own genes.

Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements

PubMed Central

Wang, Lu; Mariño-Ramírez, Leonardo

2017-01-01

Abstract Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification. PMID:27998931

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms.

PubMed

Azevedo, Ana P; Silva, Susana N; De Lima, João P; Reichert, Alice; Lima, Fernando; Júnior, Esmeraldina; Rueff, José

2017-06-01

The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog ( E. coli ) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms

PubMed Central

Azevedo, Ana P.; Silva, Susana N.; De Lima, João P.; Reichert, Alice; Lima, Fernando; Júnior, Esmeraldina; Rueff, José

2017-01-01

The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility. PMID:28599464

Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

PubMed Central

2014-01-01

Background The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile. Methods The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed. Results (CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological

No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

PubMed Central

Durieux, Gillian; Burke, Terry; Dugdale, Hannah L.

2015-01-01

Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes. PMID:26473495

Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

PubMed

Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

2014-01-01

Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

PubMed

Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2017-08-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

Polymorphic human somatostatin gene is located on chromosome 3.

PubMed Central

Naylor, S L; Sakaguchi, A Y; Shen, L P; Bell, G I; Rutter, W J; Shows, T B

1983-01-01

Somatostatin is a 14-amino-acid neuropeptide and hormone that inhibits the secretion of several peptide hormones. The human gene for somatostatin SST has been cloned, and the sequence has been determined. This clone was used as a probe in chromosome mapping studies to detect the human somatostatin sequence in human-rodent hybrids. Southern blot analysis of 41 hybrids, including some containing translocations of human chromosomes, placed SST in the q21 leads to qter region of chromosome 3. Human DNAs from unrelated individuals were screened for restriction fragment polymorphisms detectable by the somatostatin gene probe. Two polymorphisms were found: (i) an EcoRI variant located at the 3' end of the gene, found in Caucasian, U.S. Black, and Asian populations with a frequency of approximately 0.10 and (ii) a BamHI variant in the intron, which occurs in Caucasians at a frequency of 0.13. Images PMID:6133281

Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab.

PubMed

Zhang, Wu; Gordon, Michael; Press, Oliver A; Rhodes, Katrin; Vallböhmer, Daniel; Yang, Dong Yun; Park, David; Fazzone, William; Schultheis, Anne; Sherrod, Andy E; Iqbal, Syma; Groshen, Susan; Lenz, Heinz-Josef

2006-07-01

The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-765C, epidermal growth factor (EGF) A61G, epidermal growth factor receptor (EGFR) codon R497 K, EGFR CA dinucleotide repeat in intron 1, interleukin (IL)-8 T-251A and vascular endothelial growth factor (VEGF) C936 T gene polymorphisms. Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab. Using the polymerase chain reaction-restriction fragment length polymorphism method, gene polymorphisms of CCND1, COX-2, EGF, EGFR, IL-8 and VEGF were assessed from genomic DNA extracted from blood samples. A significant association was found between the CCND1 A870G polymorphism and overall survival in our 39 CRC subjects. Patients with the AA homozygous genotype survived for a median of 2.3 months [95% confidence interval (CI)=2.1-5.7], whereas those with any G allele (AG, GG genotype) survived for a median of 8.7 months (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed the cyclin D1 and EGF polymorphisms together, patients with favourable genotypes (EGF any A allele and CCND1 any G allele) showed a median survival time of 12 months (95% CI=4.8-15.2), whereas patients with any two unfavourable genotypes (EGF GG or CCND1 AA) showed a median survived time of 4.4 months (95% CI=2.1-5.7) (P=0.004, log-rank test). The findings of this pilot study suggest that the cyclin D1 A870G and the EGF A61G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab.

Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson's disease susceptibility in Chinese Han population.

PubMed

Dai, Yi; Wu, Yuquan; Li, Yansheng

2015-01-01

The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson's disease (PD) susceptibility in Chinese Han population. The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ(2) test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.

Prolactin receptor gene polymorphism and the risk of recurrent pregnancy loss: a case-control study.

PubMed

Kim, Jin Ju; Choi, Young Min; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan; Han, Ae Ra; Hwang, Kyu Ri; Hong, Min A

2018-02-01

Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student's t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss. Impact statement What is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

PubMed

Singh, Prithvi Kumar; Chandra, Girish; Bogra, Jaishri; Gupta, Rajni; Kumar, Vijay; Hussain, Syed Rizwan; Jain, Amita; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem

2016-02-01

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

Association among oxidized LDL levels, MnSOD, apolipoprotein E polymorphisms, and cardiovascular risk factors in a south Brazilian region population.

PubMed

Gottlieb, Maria G V; Schwanke, Carla H A; Santos, Adriana F R; Jobim, Paulo F; Müssel, Denise P; da Cruz, Ivana B M

2005-12-30

Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.

A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1

PubMed Central

Lattka, E.; Eggers, S.; Moeller, G.; Heim, K.; Weber, M.; Mehta, D.; Prokisch, H.; Illig, T.; Adamski, J.

2010-01-01

Fatty acid desaturases (FADS) play an important role in the formation of omega-6 and omega-3 highly unsaturated fatty acids (HUFAs). The composition of HUFAs in the human metabolome is important for membrane fluidity and for the modulation of essential physiological functions such as inflammation processes and brain development. Several recent studies reported significant associations of single nucleotide polymorphisms (SNPs) in the human FADS gene cluster with HUFA levels and composition. The presence of the minor allele correlated with a decrease of desaturase reaction products and an accumulation of substrates. We performed functional studies with two of the associated polymorphisms (rs3834458 and rs968567) and showed an influence of polymorphism rs968567 on FADS2 promoter activity by luciferase reporter gene assays. Electrophoretic mobility shift assays proved allele-dependent DNA-binding ability of at least two protein complexes to the region containing SNP rs968567. One of the proteins binding to this region in an allele-specific manner was shown to be the transcription factor ELK1 (a member of ETS domain transcription factor family). These results indicate that rs968567 influences FADS2 transcription and offer first insights into the modulation of complex regulation mechanisms of FADS2 gene transcription by SNPs. PMID:19546342

A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1.

PubMed

Lattka, E; Eggers, S; Moeller, G; Heim, K; Weber, M; Mehta, D; Prokisch, H; Illig, T; Adamski, J

2010-01-01

Fatty acid desaturases (FADS) play an important role in the formation of omega-6 and omega-3 highly unsaturated fatty acids (HUFAs). The composition of HUFAs in the human metabolome is important for membrane fluidity and for the modulation of essential physiological functions such as inflammation processes and brain development. Several recent studies reported significant associations of single nucleotide polymorphisms (SNPs) in the human FADS gene cluster with HUFA levels and composition. The presence of the minor allele correlated with a decrease of desaturase reaction products and an accumulation of substrates. We performed functional studies with two of the associated polymorphisms (rs3834458 and rs968567) and showed an influence of polymorphism rs968567 on FADS2 promoter activity by luciferase reporter gene assays. Electrophoretic mobility shift assays proved allele-dependent DNA-binding ability of at least two protein complexes to the region containing SNP rs968567. One of the proteins binding to this region in an allele-specific manner was shown to be the transcription factor ELK1 (a member of ETS domain transcription factor family). These results indicate that rs968567 influences FADS2 transcription and offer first insights into the modulation of complex regulation mechanisms of FADS2 gene transcription by SNPs.

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

Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women.

PubMed

Kim, Kyu-nam; Kim, Kwang-min; Kim, Bom-taeck; Joo, Nam-seok; Cho, Doo-yeoun; Lee, Duck-joo

2012-04-01

Hypertension (HTN) is a major determinant of various cardiovascular events. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 loci (4G/4G, 4G/5G, 5G/5G) affects the expression of this gene. The present study investigated the association between PAI-1 loci polymorphisms and HTN in Korean women. Korean women (n = 1312) were enrolled in this study to evaluate the association between PAI-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors. PAI-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis. The three genotype groups differed with respect to systolic blood pressure (P = 0.043), and diastolic blood pressure (P = 0.009) but not with respect to age, body mass index, total cholesterol, low or high density lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the PAI-1 4G allele had more hypertension significantly (PAI-1 4G/5G vs. PAI-1 5G/5G, P = 0.032; PAI-1 4G/4G vs. PAI-1 5G/5G, P = 0.034). When stratified according to PAI-1 4G/5G polymorphism, there was no significant difference in all metabolic parameters among PAI-1 genotype groups in patients with HTN as well as subjects with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 (P = 0.005), and 1.6 (P = 0.015), respectively. These findings might indicate that PAI-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population.

PubMed

Alharbi, Khalid Khalaf; Alnbaheen, May Salem; Alharbi, Fawiziah Khalaf; Hasanato, Rana M; Khan, Imran Ali

2017-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients. To investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients. Case-control study. Tertiary care center, Riyadh. Two hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis. The strength of association between the Q192R polymorphism and FH in the Saudi population. We confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05-3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13-3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09- 2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population. In conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH. Only a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

PubMed Central

Berro, Mariano; Mayor, Neema P.; Maldonado-Torres, Hazael; Cooke, Louise; Kusminsky, Gustavo; Marsh, Steven G.E.; Madrigal, J. Alejandro; Shaw, Bronwen E.

2010-01-01

Background Many genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Design and Methods We investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 mye-loablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors. Results Patients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients’ genotype, the incidences of both overall and grades II-IV acute graft-versus-host disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs. Conclusions We conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors. PMID:19713222

The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

PubMed

He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

2016-02-26

BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility.

[CCR5, CCR2, apoe, p53, ITGB3 and HFE gene polymorphism in Western Siberia long-livers].

PubMed

Ivanoshchuk, D E; Mikhaĭlova, S V; Kulikov, I V; Maksimov, V N; Voevoda, M I; Romashchenko, A G

2012-01-01

In order to estimate the distribution of some polymorphisms for the CCR5, CCR2, apoE, p53, ITGB3, and HFE genes in Russian long-livers from Western Siberia, a sample of 271 individuals (range 90-105 years) was examined. It was demonstrated that carriage of the delta32 polymorphism for the CCR5 gene, V64/polymorphism for the CCR2 gene, e2/e3/e4 for the apoE gene, L33P for the ITGB3 gene, as well as H63D and S65C polymorphisms for the HFE gene does not influence on predisposition to the longevity; carriage of the 282 Y allele for the HFE gene negatively influences on the longevity; carriage of the heterozygous genotype for the R72P polymorphism for the p53 gene correlates with the longevity of elderly people.

[Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

PubMed

Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

2008-04-01

To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

Adolescent idiopathic scoliosis and the single-nucleotide polymorphism of the growth hormone receptor and IGF-1 genes.

PubMed

Yang, Yong; Wu, Zhihong; Zhao, Taimao; Wang, Hai; Zhao, Dong; Zhang, Jianguo; Wang, Yipeng; Ding, Yaozhong; Qiu, Guixing

2009-06-01

The etiology of adolescent idiopathic scoliosis is undetermined despite years of research. A number of hypotheses have been postulated to explain its development, including growth abnormalities. The irregular expression of growth hormone and insulin-like growth factor-1 (IGF-1) may disturb hormone metabolism, result in a gross asymmetry, and promote the progress of adolescent idiopathic scoliosis. Initial association studies in complex diseases have demonstrated the power of candidate gene association. Prior to our study, 1 study in this field had a negative result. A replicable study is vital for reliability. To determine the relationship of growth hormone receptor and IGF-1 genes with adolescent idiopathic scoliosis, a population-based association study was performed. Single nucleotide polymorphisms with potential function were selected from candidate genes and a distribution analysis was performed. A conclusion was made confirming the insufficiency of an association between adolescent idiopathic scoliosis and the single-nucleotide polymorphism of the growth hormone receptor and IGF-1 genes in Han Chinese.

Association Study of Serotonin Transporter Gene Polymorphisms with Obstructive Sleep Apnea Syndrome in Chinese Han Population

PubMed Central

Yue, Weihua; Liu, Huiguo; Zhang, Jishui; Zhang, Xianghui; Wang, Xiaoping; Liu, Tieqiao; Liu, Pozi; Hao, Wei

2008-01-01

Background: Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS). Objective: To investigate the association of 5-HTT gene polymorphisms with OSAS and clinical characteristics. Methods: We genotyped the 5-HTT gene linked polymorphic region (5-HTTLPR) and a variable number of tandem repeats at intron 2 (STin2.VNTR) in 254 OSAS patients and 338 healthy controls in Chinese Han population. Results: In total sample, the 10-repeat allele of STin2.VNTR was significantly associated with OSAS (P = 0.007, OR = 1.72, 95% CI = 1.15~2.58), but no association was found in 5-HTTLPR. In male subjects, both polymorphisms showed significant association with OSAS (Allele L: P = 0.005, OR = 1.44, 95% CI = 1.11 to 1.87; Allele 10: P = 0.002, OR = 1.94, 95% CI = 1.26 to 3.00). Two haplotypes, S-12 and L-10, constructed by the above polymorphisms also revealed significant associations with OSAS (global P-values were 0.020 for total sample and 0.0006 for male subjects, respectively). Male patients carrying the haplotype S-12 showed a significantly lower apnea / hypopnea index (AHI), depressive factor, plasma 5-HT level and 5-hydroxyindolacetic acid (5-HIAA) levels, but higher episodic memory, when compared with non-S-12 carriers (P < 0.05). However, no significant differences were found in excessive daytime sleepiness or other psychological function across haplotype carriers (P > 0.05). Conclusions: These findings support that 5-HTT gene may be involved in susceptibility to OSAS, especially with sex-dependent effect. Citation: Yue W; Liu H; Zhang J; Zhang X; Wang X; Liu T; Liu P; Hao W. Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in chinese han population. SLEEP 2008;31(11):1535–1541. PMID:19014073