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1

Interaction of MTHFR C677T and A1298C, and MTR A2756G gene polymorphisms in breast cancer risk in a population in Northeast Brazil.  

PubMed

Polymorphisms in genes encoding enzymes of folate metabolism are a focus of breast cancer risk studies due of the role of these enzymes in DNA methylation, synthesis, and repair. MTHFR, encoding for 5,10-methylenetetrahydrofolate reductase, is one of the most studied genes in this regard, but findings are controversial, and the majority of studies have analyzed polymorphisms individually. In this case control study, we examined the combination of the polymorphisms MTHFR C677T and A1298C with MTR A2756G, where MTR, methionine synthase, is an important enzyme of the folate cycle in the methylation pathway. One hundred and forty-two patients with breast cancer and controls were included and the genotypes were determined using PCR-RFLP. In the population studied, individuals carrying the polymorphic allele in the heterozygous state for both enzymes, MTHFR C677T and MTR A2756G, had an increased risk [odds ratio, OR=2.77 (95% confidence interval, CI=1.19-6.52)] for disease, compared to those with the wild genotype. In addition, individuals carrying the MTR 2756 genotype AG had an increased risk when this was combined with the MTHFR 1298 genotype CC [OR=5.13 (95% CI=0.87-38.82)]. No significant results were found from the analyses associating the MTHFR C677T and A1298C genotypes. However, when stratifying the patients by age (50 years old as the cut-off), patients over 50 years old had greater risk, with the presence of both MTHFR polymorphisms in the heterozygous state [OR=5.33 (95% CI=1.42-21.03)]. This study points out the importance of the interactions between the MTHFR C677T, MTHFR A1298C and MTR A2756G polymorphisms, and also highlights the relevance of the MTR A2756G polymorphism and age in breast cancer risk. PMID:23155246

de Cássia Carvalho Barbosa, Rita; da Costa, Débora Menezes; Cordeiro, Denise Ellen Francelino; Vieira, Ana Patricia Freitas; Rabenhorst, Silvia Helena Barem

2012-11-01

2

Role of C677T and A1298C MTHFR, A2756G MTR and -786 C/T eNOS Gene Polymorphisms in Atrial Fibrillation Susceptibility  

PubMed Central

Background Hyperhomocysteinemia has been suggested to play a role in the NonValvular Atrial Fibrillation (NVAF) pathogenesis. Polymorphisms in genes coding for homocysteine (Hcy) metabolism enzymes may be associated with hyperhomocysteinemia and NVAF. Methodologies 456 NVAF patients and 912 matched controls were genotyped by an electronic microchip technology for C677T and A1298C MTHFR, A2756G MTR, and -786C/T eNOS gene polymorphisms. Hcy was determined by an immunoassay method. Principal Findings The genotype distribution of the four polymorphisms as well as genotype combinations did not differ in patients and controls. Hcy was higher in patients than in controls (15.2, 95%CI 14.7–15.7 vs 11.3, 95%CI 11.0–11.6 µmol/L; p<0.0001). In both populations, a genotype-phenotype association (p<0.0001) between Hcy and C677T MTHFR polymorphism was observed; in controls a significant (p?=?0.029) association between tHcy and ?786C/T eNOS polymorphism was also observed. At the multivariate analysis the NVAF risk significantly increased in the upper quartiles of Hcy compared to the lowest: OR from 2.8 (1.68–4.54 95%CI) in Q2 to 12.9 (7.96–21.06 95%CI) in Q4. Conclusions Our data demonstrated the four polymorphisms, although able, at least in part, to affect Hcy, were not associated with an increased risk of NVAF per se or in combination.

Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Sestini, Ilaria; Saracini, Claudia; Sticchi, Elena; Gensini, Francesca; Fatini, Cinzia; Abbate, Rosanna; Gensini, Gian Franco

2007-01-01

3

Genetic Polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) Genes Associated With Pathological Characteristics of Prostate Cancer in the Ecuadorian Population.  

PubMed

INTRODUCTION:: The methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) enzymes act in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G and MTRR A66G, cause alteration in the homocysteine levels and reduced enzymatic activity that generates deficiency in the assimilation of folates associated with DNA damage; that is, why it is important to know if the single nucleotide polymorphisms are associated with the pathological characteristics and development of prostate cancer, through a case-control retrospective study. METHODS:: DNA was extracted from 110 healthy and 104 affected men. The genotypes were determined by means of the polymerase chain reaction-restriction fragment length polymorphism and confirmed with genomic sequencing. RESULTS:: We found significant association between the genotypes of the MTHFR C677T polymorphism: C/T (odds ratio [OR] = 2.2; 95% confidence interval [CI] = 1.3-3.9; P = 0.008) and C/T + T/T (OR = 2.2; 95% CI = 1.3-3.9; P = 0.009) with the risk of prostate cancer development, and a slight association with MTRR A66G. Regarding pathological characteristics, we found significant risk between the C/T + T/T genotypes and the Gleason score (7-10) of poorly differentiated carcinoma (OR = 5.2; 95% CI = 1.7-16.2; P = 0.007). On the other hand, a significant association between A1298C, A66G, and A2756G with the pathological characteristics was not found (P > 0.05). CONCLUSIONS:: The MTHFR C677T polymorphism has significant effects on susceptibility to prostate cancer in Ecuadorian population, especially with the Gleason grade. PMID:23459165

López-Cortés, Andrés; Jaramillo-Koupermann, Gabriela; Muñoz, María J; Cabrera, Alejandro; Echeverría, Carolina; Rosales, Felipe; Vivar, Nicolás; Paz-Y-Miño, César

2013-03-01

4

Methionine synthase A2756G and methylenetetrahydrofolate reductase A1298C polymorphisms are not risk factors for idiopathic venous thromboembolism  

Microsoft Academic Search

Hyperhomocysteinemia is a defined risk factor for venous thromboembolism (VTE). Several polymorphisms of genes encoding for enzymes acting in the remethylation pathway of homocysteine metabolism, ie, methionine synthase (MS) A2756G, methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C, can cause increased homocysteine levels particularly in patients with deficiencies of folic acid, vitamin B6, or B12 and hence be potential risk factors

Ophira Salomon; Nurit Rosenberg; Ariella Zivelin; David M Steinberg; Nurit Kornbrot; Rima Dardik; Aida Inbal; Uri Seligsohn

2001-01-01

5

Role of polymorphism of methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G and breast cancer risk.  

PubMed

Breast cancer (BC) is one of the most common causes of death among women, and second in Iran. The objectives of this study were to determine the frequency of methyltetrahydrofolate-homocysteine methyltransferase (MTR) 2756 gene polymorphism in patients with breast cancer. For the first time, we evaluated these polymorphisms and effects on the breast cancer risk association in an Iranian sporadic population-based case-control study of 282 breast cancer cases and 310 controls using a PCR-RFLP-based assay. Analyses of affected and controls show that homozygote genotype MTR 2756 AA has the highest frequency in both groups (33.3 in patients). Genotype MTR 2756 GG was the highest risk factor in our population [AG/GG odds ratio, 0.329 (95% CI: 0.146-0.741) p = 0.006, AA/AG, OR, 2.316, 95% CI: 1.509-3.555, p = 0.001, AA/GG odds ratio, 0.761 (95% CI: 0.363-1.595) p = 0.297]. There was a significant association of breast cancer risk with MTR 2756 GG and AA polymorphism. PMID:24166605

Hosseini, M

2013-11-01

6

MTHFR C677T and MTR A2756G polymorphisms and the homocysteine lowering efficacy of different doses of folic acid in hypertensive Chinese adults  

PubMed Central

Background This study aimed to investigate if the homocysteine-lowering efficacy of two commonly used physiological doses (0.4 mg/d and 0.8 mg/d) of folic acid (FA) can be modified by individual methylenetetrahydrofolate reductase (MTHFR) C677T and/or methionine synthase (MTR) A2756G polymorphisms in hypertensive Chinese adults. Methods A total of 480 subjects with mild or moderate essential hypertension were randomly assigned to three treatment groups: 1) enalapril only (10 mg, control group); 2) enalapril-FA tablet [10:0.4 mg (10 mg enalapril combined with 0.4 mg of FA), low FA group]; and 3) enalapril-FA tablet (10:0.8 mg, high FA group), once daily for 8 weeks. Results After 4 or 8 weeks of treatment, homocysteine concentrations were reduced across all genotypes and FA dosage groups, except in subjects with MTR 2756AG /GG genotype in the low FA group at week 4. However, compared to subjects with MTHFR 677CC genotype, homocysteine concentrations remained higher in subjects with CT or TT genotype in the low FA group (P < 0.05 for either of these genotypes) and TT genotype in the high FA group (P < 0.05). Furthermore, subjects with TT genotype showed a greater homocysteine-lowering response than did subjects with CC genotype in the high FA group (mean percent reduction of homocysteine at week 8: CC 10.8% vs. TT: 22.0%, P = 0.005), but not in the low FA group (CC 9.9% vs. TT 11.2%, P = 0.989). Conclusions This study demonstrated that MTHFR C677T polymorphism can not only affect homocysteine concentration at baseline and post-FA treatment, but also can modify therapeutic responses to various dosages of FA supplementation.

2012-01-01

7

The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma  

PubMed Central

The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy±surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes (MTHFR C677T, MTR A2756G, TS tandem repeat polymorphism) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy. The genotypes were correlated with tumour response to polychemotherapy, radiochemotherapy and with overall survival. Tumours with the MTR wild-type genotype (2756AA) showed a median survival time of 16 months, whereas tumours with an MTR variant genotype (2756AG/2756GG) showed a median survival time of 42 months (P=0.0463). No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene. Among tumours treated with radiochemotherapy and subsequent resection, MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype (P=0.0442). In contrast, no significant relationship between clinically determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed. In conclusion, pretherapeutic determination of the MTR A2756G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas. Determination of MTHFR C677T and TS tandem repeat polymorphism has no predictive value.

Sarbia, M; Stahl, M; von Weyhern, C; Weirich, G; Puhringer-Oppermann, F

2006-01-01

8

Evaluation of the MTHFR A1298C variant in leukoaraiosis.  

PubMed

Vascular demyelinization of the white matter of the brain is referred to as leukoaraiosis (LA). This very frequent entity is associated with a cognitive decline, thereby resulting in a deteriorating quality of life. Besides poorly controlled hypertension and aging, its development is reported to be associated with an elevated serum homocysteine level. Although the methylenetetrahydrofolate reductase (MTHFR) C677T genetic variant is associated with an elevated serum homocysteine level, it has not been proved to be an independent risk factor for LA. The aim of the present study was to examine whether the MTHFR A1298C genetic variant, which is also believed to be unfavorable, is associated with the presence of LA. The clinical and genetic data on 198 LA patients and 235 neuroimaging alteration-free controls were analyzed. The presence of the A1298C or the 1298CC variant was calculated to be a risk factor for LA, as compared with the absence of both of them. The clustering of the heterozygous A1298C and C677T variants was proved to involve the risk of LA. Our results suggest that the MTHFR A1298C variant confers an independent genetic risk of LA, and this pathological role may be amplified by the MTHFR C677T variant. PMID:21845428

Szolnoki, Zoltan; Szaniszlo, Istvan; Szekeres, Marta; Hitri, Krisztina; Kondacs, Andras; Mandi, Yvette; Nedo, Erika; Somogyvari, Ferenc

2011-08-16

9

Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment  

Technology Transfer Automated Retrieval System (TEKTRAN)

To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. We screened 224 subjects (52% female, mean age 39 +/- 11 years) with SCID-diagnosed major...

10

Role of methylenetetrahydrofolate reductase A1298C polymorphism in cerebral venous thrombosis.  

PubMed

The association between the methylenetetrahydrofolate reductase (MTHFR) gene and cerebral venous thrombosis (CVT) remains controversial. This study principally investigated the potential role of the MTHFR A1298C variant and CVT. The genotyping of the A1298C variant of the MTHFR gene was performed in 35 CVT patients and 200 healthy controls. The frequency of A1298C genotype among CVT patients was significantly higher compared with controls (P?A1298C variant and CVT. Large study populations would be required to understand the contribution of this marker in the risk of CVT. PMID:23314385

Fekih-Mrissa, Najiba; Klai, Sarra; Mrad, Meriem; Zaouali, Jamel; Sayeh, Aycha; Nsiri, Brahim; Gritli, Nasreddine; Mrissa, Ridha

2013-03-01

11

Two cousins with neonatal stroke, PAI-1 4G variant and MTHFR A1298C mutation.  

PubMed

The authors describe 2 female cousins with neonatal stroke. One was heterozygous for the plasminogen activator inhibitor-1 4G variant and compound heterozygous for the A1298C and C677T methylenetetrahydrofolate reductase mutations. Her cousin was homozygous for the plasminogen activator inhibitor-1 4G variant and heterozygous for the methylenetetrahydrofolate reductase A1298C and factor V Leiden mutations. PMID:17641264

Golomb, Meredith R; Heiny, Mark; Garg, Bhuwan P

2007-06-01

12

Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians  

Microsoft Academic Search

We have investigated the incidence of the C677T and A1298C methylene tetrahydrofolate reductase (MTHFR) gene single nucleotide polymorphisms (SNPs) in the South Indian Tamil Nadu population with a total number of 72 individuals. The MTHFR genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis. Homozygosity for the MTHFR A1298C SNP was detected in 15.3% (11\\/72) of

T. Angeline; Nirmala Jeyaraj; Selena Granito; Gregory J. Tsongalis

2004-01-01

13

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility  

Microsoft Academic Search

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast\\u000a cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline,\\u000a PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between\\u000a the MTHFR A1298C polymorphism and breast

Li-Xin QiuJian; Jian Zhang; Wen-Hua Li; Qun-Ling Zhang; Hui Yu; Bi-Yun Wang; Lei-Ping Wang; Jia-Lei Wang; Hui-Jie Wang; Xiao-Jian Liu; Zhi-Guo Luo; Xiang-Hua Wu

2011-01-01

14

Further evidence that methylenetetrahydrofolate reductase A1298C polymorphism is a risk factor for schizophrenia  

Microsoft Academic Search

Previous work suggests that the methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphism A1298C may be a risk factor for schizophrenia. In this study, the genetic association between the\\u000a MTHFR A1298C polymorphism and schizophrenia was investigated in 379 patients with schizophrenia and 380 age- and sex-matched controls\\u000a subjects. The results showed an association between the 1298C allele and the disorder (OR 1.39,

Chen ZhangBin; Bin Xie; Yasong Du; Wenhong Cheng; Yiru Fang; Shunying Yu

2010-01-01

15

Prevalence of MTHFR gene polymorphisms (C677T and A1298C) among Tamilians.  

PubMed

We have investigated the incidence of the C677T and A1298C methylene tetrahydrofolate reductase (MTHFR) gene single nucleotide polymorphisms (SNPs) in the South Indian Tamil Nadu population with a total number of 72 individuals. The MTHFR genotyping was performed using the polymerase chain reaction followed by restriction enzyme analysis. Homozygosity for the MTHFR A1298C SNP was detected in 15.3% (11/72) of the individuals tested, and 47.2% (34/72) were heterozygous for this SNP. Homozygosity for the C677T MTHFR SNP was detected in 1.38%(1/72), and the frequency of the C677T heterozygotes was 18.1%(13/72). When we analyzed the combined frequency of the two SNPs, the frequency of double heterozygosity was19.6%, and the frequency of double homozygosity was completely absent among the study group. The 'C' allele frequency for MTHFR A1298C was 0.389, and the 'T' allele frequency for C677T mutation was 0.104. Out of the 72 individuals included in the study, 52 were acute myocardial infarction (AMI) patients and 20 were healthy individuals with no documented history of heart disease. The results of this study indicate that the MTHFR A1298C SNP is more prevalent among the Tamilians when compared to the MTHFR C677T SNP, suggesting a possible role of MTHFR A1298C in the pathogenesis of heart diseases. PMID:15351230

Angeline, T; Jeyaraj, Nirmala; Granito, Selena; Tsongalis, Gregory J

2004-10-01

16

Comparing Techniques for the Identification of the MTHFR A1298C Polymorphism  

PubMed Central

The restriction fragment length polymorphism (RFLP) technique with the MboII enzyme is used by a number of researchers as a methodology for the identification of the genetic polymorphism MTHFR A1298C. However, the reliability of this enzyme for genotyping this polymorphism has been questioned, since the silent polymorphism T1317C, located close to the polymorphic region A1298C on gene MTHFR, also has a recognition site for MboII. Thus, the fragments formed by the digestion of MboII present similar sizes, making it difficult to differentiate the allele MTHFR 1298A in the presence of the allele MTHFR 1317C. Hence, we investigated the A1298C polymorphism in a Brazilian population of renal transplant patients, using the RFLP technique with digestion by Mbo II and using sequencing, in order to examine the concordance between the two techniques. Our results showed an 8.6% difference in genotyping between RFLP and sequencing, but the statistical concordance test presented a kappa coefficient equal to 0.81 (CI 95% 0.74–88), which indicates a virtually perfect concordance, according to the criterion of Landis and Koch. Therefore, we concluded that the RFLP technique is concordant with automated sequencing in the detection of polymorphism A1298C under our laboratory conditions.

de Alvarenga, Maria Paula Sanches; Pavarino-Bertelli, Erika Cristina; Goloni-Bertollo, Eny Maria

2008-01-01

17

Association of the MTHFR A1298C Variant with Unexplained Severe Male Infertility  

Microsoft Academic Search

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group

Abdelmajid Eloualid; Omar Abidi; Majida Charif; Brahim El houate; Houda Benrahma; Noureddine Louanjli; Elbakkay Chadli; Maria Ajjemami; Abdelhamid Barakat; Anu Bashamboo; Ken McElreavey; Houria Rhaissi; Hassan Rouba

2012-01-01

18

Influence of maternal MTHFR A1298C polymorphism on the risk in offspring of schizophrenia  

Microsoft Academic Search

Several lines of evidence have suggested that two functional methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, C677T and A1298C, may be implicated in the etiology of schizophrenia. We examined these MTHFR polymorphisms in 111 families, composed of a patient and their parents, as well as 143 mothers of patients with schizophrenia and 235 age-matched mothers who had healthy children. The maternal MTHFR

Chen Zhang; Bin Xie; Yiru Fang; Wenhong Cheng; Yasong Du; Dongxiang Wang; Shunying Yu

2010-01-01

19

Association of the MTHFR A1298C variant with unexplained severe male infertility.  

PubMed

The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR?=?3.372, 95% confidence interval CI?=?1.27-8.238; p?=?0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants. PMID:22457816

Eloualid, Abdelmajid; Abidi, Omar; Charif, Majida; El Houate, Brahim; Benrahma, Houda; Louanjli, Noureddine; Chadli, Elbakkay; Ajjemami, Maria; Barakat, Abdelhamid; Bashamboo, Anu; McElreavey, Ken; Rhaissi, Houria; Rouba, Hassan

2012-03-23

20

Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease  

Microsoft Academic Search

Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked\\u000a with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover,\\u000a data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine\\u000a in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and

Lakhdar Ghazouani; Nesrine Abboud; Nabil Mtiraoui; Walid Zammiti; Faouzi Addad; Haitham Amin; Wassim Y. Almawi; Touhami Mahjoub

2009-01-01

21

MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer.  

PubMed

5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95% CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6; 95% CI, 0.4-0.9) but not men. When the polymorphisms were considered individually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12), and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = <.01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation. PMID:14973104

Curtin, Karen; Bigler, Jeannette; Slattery, Martha L; Caan, Bette; Potter, John D; Ulrich, Cornelia M

2004-02-01

22

A literature review of MTHFR (C677T and A1298C polymorphisms) and cancer risk.  

PubMed

5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folate metabolism. This enzyme is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). The C677T and A1298C are MTHFR polymorphisms that decrease in vitro MTHFR enzyme activity. Folate metabolism plays a key role in cell metabolism. These reactions are associated with purine-pyrimidine synthesis: DNA, RNA, and protein methylation. Polymorphism is also a factor in biodiversity, and be affected by ethnic heritage and geographic locale. In the case of unknown outcomes, not only should all geographical regions be investigated to ascertain biodiversity, but all populations as well to fully understand the variations in the effect. PUBMED was searched from January 2006 to December 2011 to develop an investigatory pursuit strategy. MTHFR, cancer, C677T, A1298C, and polymorphisms were key words used to focus the search. The literature review included all published relevant cancer types and MTHFR polymorphisms for that 5 years period. All selected polymorphisms data for cancer types was listed in tables for easy access and retrieval. PMID:23076526

Izmirli, Muzeyyen

2012-10-19

23

Association of MTHFR C677T and A1298C gene polymorphisms with hypertension  

PubMed Central

Objectives To check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region. Subjects and methods Participants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphisms Results Total cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2–3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3–5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3–3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively). Conclusion This work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.

Alghasham, Abdullah; Settin, Ahmad A; Ali, Ahmad; Dowaidar, Moataz; Ismail, Hisham

2012-01-01

24

C677T and A1298C Mutations in the MTHFR Gene and Survival in Colorectal Cancer  

Microsoft Academic Search

Background and aims: Our preliminary results laboratory have shown some association between C677T and A1298C MTHFR mutations and factors influencing survival in colorectal cancer. We studied the survival of patients with colorectal cancer depending on the initial Dukes- MAC stage of the disease at the time of diagnosis and the MTHFR mutation present. Methods: We randomly selected 69 patients with

Gelu Osian; Lucia Procopciuc; Liviu Vlad; Cornel Iancu; Teodora Mocan; Lucian Mocan

25

Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease.  

PubMed

Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover, data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and gender-matched healthy subjects. Significantly higher frequency of 677T allele and homozygous 677T/T genotype were seen in patients vs. control subjects; the distribution of A1298C alleles and genotypes being comparable in the two groups. Specific MTHFR haplotypes comprising 677C/1298A (P < 0.001) and 677T/1298A (P < 0.001) were negatively and positively associated with CAD, respectively. Plasma homocysteine concentration was significantly higher in 677T/T genotype with respect to 677C/C and 677C/T genotypes in patients and controls, but homocysteine levels were generally comparable between both groups. Univariate analysis identified 677T/1298A (P = 0.033) haplotype to be positively associated with CAD, which remained significant by multivariate analysis after adjusting for a number of covariates (P = 0.038). MTHFR C677T, but not A1298C SNPs, is associated with CAD and with elevated homocysteine levels in a Tunisian population. The negative and positive association of the 1298A allele with CAD being indicative of a neutral (absent) effect of the A1298C SNP on disease pathogenesis. PMID:18204887

Ghazouani, Lakhdar; Abboud, Nesrine; Mtiraoui, Nabil; Zammiti, Walid; Addad, Faouzi; Amin, Haitham; Almawi, Wassim Y; Mahjoub, Touhami

2008-01-19

26

MTHFR C677T and A1298C polymorphisms are risk factors for Down’s syndrome in Indian mothers  

Microsoft Academic Search

Downs syndrome (DS), a chromosomal disorder due to trisomy 21, results mostly from nondisjunction in maternal meiosis. The present case-control study examined the association of genetic polymorphisms with predisposition to nondisjunction. Two common polymorphisms (SNPs), C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, are known to lower the activity of this enzyme. Three hundred and

Amit Kumar Rai; Satya Singh; Stuti Mehta; Ashok Kumar; L. K. Pandey; Rajiva Raman

2006-01-01

27

A Common Mutation A1298C in Human Methylenetetrahydrofolate Reductase Gene: Association with Plasma Total Homocysteine and Folate Concentrations1  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocys- teine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related

Gideon Friedman; Netta Goldschmidt; Yechiel Friedlander; Arie Ben-Yehuda; Jacob Selhub; Sharona Babaey; Malka Mendel; Miriam Kidron; Hanoch Bar-On

28

Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia  

Microsoft Academic Search

Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic\\u000a polymorphisms and\\/or inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR\\u000a polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing\\u000a gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar

D. Caccamo; S. Condello; G. Gorgone; G. Crisafulli; V. Belcastro; S. Gennaro; P. Striano; F. Pisani; R. Ientile

2004-01-01

29

Methylenetetrahydrofolate reductase C677T and A1298C variants do not affect ongoing pregnancy rates following IVF  

Microsoft Academic Search

BACKGROUND: There is concern that IVF could compromise normal imprinting and methylation of DNA. Methyl- enetetrahydrofolate reductase (MTHFR) regulates the flow of folic acid-derived, one-carbon moieties for methylation and is critical to early embryonic development. Therefore, we hypothesized that common polymorphisms in MTHFR could associate with IVF outcome. METHODS: MTHFR C677T and A1298C polymorphism genotyping was per- formed on 374

A. T. Dobson; R. M. Davis; M. P. Rosen; S. Shen; P. F. Rinaudo; J. Chan; M. I. Cedars

2006-01-01

30

MTHFR C677T and A1298C polymorphisms are risk factors for Down's syndrome in Indian mothers.  

PubMed

Down's syndrome (DS), a chromosomal disorder due to trisomy 21, results mostly from nondisjunction in maternal meiosis. The present case-control study examined the association of genetic polymorphisms with predisposition to nondisjunction. Two common polymorphisms (SNPs), C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, are known to lower the activity of this enzyme. Three hundred and fourteen mothers (with DS children and controls), mostly from the eastern states of India, were genotyped for the two above-mentioned SNPs. Significant association with both of these SNPs were detected, more specifically, in the mothers of DS children homozygous for the polymorphic alleles 677 T and 1298 C. The relative risk of T (C677T) and C (A1298C) homozygosity in mothers for DS-affected pregnancy was 7 (OR 7.67, 95% CI 1.67-35.08, P=0.003) and 4 (OR 4.40, 95% CI 1.45-13.26, P=0.008), respectively. Moreover, all 677TT mothers studied were less than 31 years of age, whereas no correlation with maternal age was observed for A1298C genotypes. Interestingly, all of the young 677TT mothers had either a first- or secondborn child with DS. Thus, this study reports that young Indian mothers with TT genotypes are genetically predisposed to nondisjunction due to abnormal folate metabolism. PMID:16489479

Rai, Amit Kumar; Singh, Satya; Mehta, Stuti; Kumar, Ashok; Pandey, L K; Raman, Rajiva

2006-02-18

31

Methylenetetrahydrofolate reductase polymorphisms, C677T and A1298C, are associated with methotrexate-related toxicities in Korean patients with rheumatoid arthritis  

Microsoft Academic Search

We investigated associations between the methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and methotrexate\\u000a (MTX)-related toxicities in Korean patients with rheumatoid arthritis (RA) taking MTX. One hundred sixty-seven patients with\\u000a RA were enrolled in a cross-sectional study and genotyped for the single-nucleotide polymorphisms C677T and A1298C in MTHFR.\\u000a Alleles, genotypes, and haplotypes of the C677T and A1298C polymorphisms were not

Jung-Yoon Choe; Hwajeong Lee; Hyun-Young Jung; Sung-Hoon Park; Sang-Cheol Bae; Seong-Kyu Kim

32

Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects  

Microsoft Academic Search

Background: Methylenetetrahydrofolate reductase (MTHFR) deficiency leads to impairment in folate metabolism and is implicated as a risk factor for neural tube defects (NTDs). Both C677T and A1298C MTHFR mutations are associated with NTDs, in some populations. Methods: The frequencies of the C677T and A1298C MTHFR mutations were determined in 25 children with NTDs, case mothers and 75 healthy individuals from

Andrea L. A Cunha; Mario H Hirata; Chong A Kim; Elvira M Guerra-Shinohara; Kymio Nonoyama; Rosario D. C Hirata

2002-01-01

33

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses  

Microsoft Academic Search

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were

N Mtiraoui; L Ghazouani; R R Finan; W Y Almawi; T Mahjoub

2006-01-01

34

Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: The A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal)  

Microsoft Academic Search

Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on

Ana I. Freitas; Isabel Mendonça; Graça Guerra; Maria Brión; Roberto P. Reis; Angel Carracedo; António Brehm

2008-01-01

35

Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer  

Microsoft Academic Search

Authors report the results of four meta-analyses of studies that examined the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and head and neck cancer (nine studies, 2076 cases and 4834 controls for C677T; four studies, 1439 cases and 3941 controls for A1298C), and lung cancer (ten studies, 5274 cases and 7435 controls for C677T; seven studies, 5098 cases

Stefania Boccia; Paolo Boffetta; Paul Brennan; Gualtiero Ricciardi; Francesco Gianfagna; Keitaro Matsuo; Cornelia M. van Duijn; Rayjean J. Hung

2009-01-01

36

Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an examination of C677T and A1298C mutations.  

PubMed

Although rare in children, stroke is becoming increasingly recognized as an important cause of morbidity and mortality with an annual incidence of approximately 3 per 100,000 per year. While several studies have documented the underlying mechanisms and pathogenesis related to stroke in adults, including genetic and acquired prothrombotic conditions, the data available on similar conditions in children is limited. Evidence suggests that mutations in methylenetetrahydrofolate reductase (MTHFR) appear to be linked with hyperhomocysteinemia (HHC) and cerebral-thrombotic events in children. While the C677T common missense mutation is the best-characterized MTHFR polymorphism, another common missense mutation, A1298C also exists. A recent study of children demonstrated that the homozygous form of C677T polymorphism occurred two-times as often in those with stroke versus healthy controls. In our retrospective chart review of 33 children seen at Children's Hospital of Orange County from January 1, 2000 to September 30, 2003 with the diagnosis of stroke, we examined both the C677T and A1298C polymorphisms for occurrence and type. In the subset (n=21), which excluded those with a confounding disorder, we observed a significant increase in the frequency of A1298C and C677T homozygosity (0.25 [p=0.01] and 0.20 [p=0.100], respectively); expected rate: (0.06 and 0.08, respectively). Our observed rates of heterozygosity for both MTHFR mutations (0.35 and 0.40, respectively) were consistent with expected rates (0.28 and 0.38, respectively). In all subjects, homocysteine (HC) levels were normal. The results of our study suggest that mutations in MTHFR are associated with pediatric stroke. However, additional studies are required to confirm our findings and to determine if this relationship is causal. PMID:16282888

Rook, James L; Nugent, Diane J; Young, Guy

2005-11-01

37

Population distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C risk alleles for methotrexate toxicity in Israel.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a central regulatory enzyme in the folate pathway. Two non-synonymous single nucleotide polymorphisms in MTHFR, C677T (rs1801133) and A1298C (rs1801131) have been associated with reduced MTHFR enzyme activity. These polymorphisms, especially C677T, appear to be linked with methotrexate-related toxicity, particularly hepatotoxicity; thus, pretreatment identification of individuals carrying these polymorphisms may be of clinical relevance. The purpose of this study was to determine the frequency and distribution of MTHFR polymorphic variants, known to functionally impair MTHFR activity, in the highly heterogeneous Israeli population. MTHFR genotyping was carried out in the representatives of three major demographic groups in Israel by PCR-restriction fragment length polymorphism and high-resolution melting. The relative distribution of variant alleles 677T and 1298C was found to be similar in individuals of Jewish, Druze and Arab Moslem descent (p = 0.09). However, Ashkenazi Jews displayed a 1.9-fold higher frequency of variant 677T and a 1.8-fold lower frequency of variant 1298C compared to non-Ashkenazi Jews (p < 0.001). Distinct differences in the relative frequencies of both polymorphisms were also found between Ashkenazi Jews and Druze (p < 0.01 for C677T, p < 0.01 for A1298C) or Ashkenazi Jews and Arab Moslem (p < 0.01 for C677T, p < 0.05 for A1298C). These data underscore the importance of geographic genetic analysis for a better understanding of human pharmacotherapy and personalized medicine. PMID:22847291

Efrati, Edna; Elkin, Hela; Nahum, Sagi; Krivoy, Norberto

2012-07-31

38

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies. PMID:15546509

Yin, Guang; Kono, Suminori; Toyomura, Kengo; Hagiwara, Tomoko; Nagano, Jun; Mizoue, Tetsuya; Mibu, Ryuichi; Tanaka, Masao; Kakeji, Yoshihiro; Maehara, Yoshihiko; Okamura, Takeshi; Ikejiri, Koji; Futami, Kitaroh; Yasunami, Yohichi; Maekawa, Takafumi; Takenaka, Kenji; Ichimiya, Hitoshi; Imaizumi, Nobutoshi

2004-11-01

39

Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population  

PubMed Central

Background: Researchers have determined that Indians face a higher risk of heart disease, despite the fact that nearly half of them are vegetarians and lack many of the other traditional risk factors. In the below-30 age group, coronary artery disease mortality among Indians is three-fold higher than in the whites in United Kingdom and ten-fold higher than the Chinese in Singapore. High levels of homocysteine have been widely linked to the early onset of heart diseases in other populations, although a definite proof among Indians is lacking, which needs to be investigated by way of screening for factors responsible for high homocysteine levels. Objective: To screen for genetic factors responsible for hyperhomocysteinemia and the risk for premature coronary artery disease. Materials and Methods: A total of 100 individuals with proven premature coronary artery disease and 200 age-and-sex matched controls were screened for polymorphisms in Methylenetetrahydrofolate reductase (MTHFR) (C677T) Methionine synthase (MS) genes (A2756G, C2758G), and the B12 and Folate levels were estimated. Results: Results from the mutational analysis revealed that in the study group, seven individuals had a polymorphism for the C677T allele in the MTHFR gene (one homozygous and six heterozygous) (Fischer's Exact test P > 0.046) (OR: 0.2711 95% CI 0.0774 to 0.9491). Six were heterozygous for the A2756G polymorphism in the MS gene (Fischer's Exact test P > 0.0012). None showed a polymorphism at the C2758G allele in the MS gene. Four controls showed heterozygosity for the C677T polymorphism and none for the MS gene. The B12 and Folate levels were significantly lower in the study group as compared to the controls. Conclusions: It is important to know which factors determine the total homocysteine concentrations. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the total homocysteine concentrations, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors.

Kanth, V. V. Ravi; Golla, Jaya Prakash; Sastry, B. K. S; Naik, Sudhir; Kabra, Nitin; Sujatha, Madireddi

2011-01-01

40

Severe arterial thrombophilia associated with a homozygous MTHFR gene mutation (A1298C) in a young man with Klinefelter syndrome.  

PubMed

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It may be associated with an increased risk for venous thrombosis and thromboembolism, which is partially explained by hypofibrinolysis due to androgen deficiency. Additional genetic or acquired thrombophilic states have been shown in KS patients complicated with venous thrombosis as isolated case reports. Arterial thrombotic events had not been previously reported in KS. In this study, a young man with KS who developed acute arterial thrombosis during testosterone replacement therapy is presented. He was homozygous for the A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. PMID:18160591

Ozbek, Mustafa; Oztürk, M Akif; Ureten, Kemal; Ceneli, Ozcan; Erdogan, Mehmet; Haznedaroglu, Ibrahim C

2007-12-26

41

Polymorphisms of MTHFR C677T and A1298C association with oral carcinoma risk: a meta-analysis.  

PubMed

Investigations regarding association of MTHFR polymorphisms with oral carcinoma risk have yielded inconclusive results. Thus, meta-analyses were performed. Results showed that no associations of C677T polymorphisms with oral carcinoma were observed for the overall data. In subgroup analyses by drinking status, homozygous TT alleles exhibited elevated oral cancer susceptibility in heavy drinkers. For A1298C polymorphism, CC alleles presented a possible preventive role for oral cancer. Collectively, results suggest that MTHFR 677TT polymorphism might be a low-penetrant risk factor for oral carcinoma only in heavy drinkers. Conversely, 1298CC alleles might play a preventive role for oral cancer. PMID:22536935

Zhuo, Xianlu; Ling, Junjun; Zhou, Yan; Zhao, Houyu; Song, Yufeng; Tan, Yinghui

2012-04-26

42

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with male infertility: a meta-analysis.  

PubMed

Published data on the association between the methylenetetrahydrofolate reductase (MTHFR) gene A1298C (rs1801131) polymorphism and male infertility risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of seven case-control studies including 1633 cases and 1735 controls were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of the C1298 allele (C vs. A) was significantly associated with susceptibility to male infertility (OR = 1.12, 95% CI = 1.00-1.26). A subgroup analysis of the subjects showed that MTHFR 1298C was associated with significant increased risk of azoospermia in homozygote comparison (CC vs. AA) and recessive mode (CC vs. AA/AC) (OR = 1.66 for CC vs. AA genotype; OR = 1.67 for CC vs. AA/AC genotype). However, no statistically significant increased risk of oligoasthenoteratozoospermia was found in any of the genetic models. In conclusion, this meta-analysis supports that the MTHFR A1298C polymorphism is capable of causing male infertility susceptibility, especially azoospermia. PMID:22175540

Shen, Ouxi; Liu, Renping; Wu, Wei; Yu, Lugang; Wang, Xinru

2012-01-01

43

Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos.  

PubMed

The pathogenesis of spontaneous abortion is complex, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms are commonly associated with defects in folate dependent homocysteine metabolism and have been implicated as risk factors for recurrent embryo loss in early pregnancy. In the present study we have determined the prevalence of combined MTHFR C677T and A1298C polymorphisms in DNA samples from spontaneously aborted embryos (foetal death between sixth and twentieth week after conception) and adult controls using solid-phase minisequencing technique. There was a significant odds ratio of 14.2 (95% CI 1.78-113) in spontaneously aborted embryos comparing the prevalence of one or more 677T and 1298C alleles vs the wild type combined genotype (677CC/1298AA), indicating that the MTHFR polymorphisms may have a major impact on foetal survival. Combined 677CT/1298CC, 677TT/1298AC or 677TT/1298CC genotypes, which contain three or four mutant alleles, were not detected in any of the groups, suggesting complete linkage disequilibrium between the two polymorphisms. The present finding of high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos emphasises the potential protective role of periconceptional folic acid supplementation. PMID:11938441

Zetterberg, Henrik; Regland, Björn; Palmér, Mona; Ricksten, Anne; Palmqvist, Lars; Rymo, Lars; Arvanitis, Demetrios A; Spandidos, Demetrios A; Blennow, Kaj

2002-02-01

44

The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity.  

PubMed

The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity.Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ±12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined.The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events.In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA. PMID:22046205

Ta?ba?, Ozgür; Borman, P?nar; Gürhan Karabulut, Halil; Tükün, Ajlan; Yorganc?o?lu, Rezan

2011-10-14

45

The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity  

PubMed Central

The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity. Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ±12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined. The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA.

Tasbas, Ozgur; Borman, P?nar; Gurhan Karabulut, Halil; Tukun, Ajlan; Yorganc?oglu, Rezan

2011-01-01

46

Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthritis treated with methotrexate: implication with elevation of transaminases  

Microsoft Academic Search

Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies

J P Mena; M Salazar-Páramo; L González-López; J I Gámez-Nava; L Sandoval-Ramirez; J D Sánchez; L E Figuera; F J Muñoz-Valle; M Vazquez del Mercado; I P Dávalos

2011-01-01

47

MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples,

Fakhraddin Naghibalhossaini; Pooneh Mokarram; Islam Khalili; Mohammad Vasei; Seyed Vahid Hosseini; Hassan Ashktorab; Mozhgan Rasti; Kourosh Abdollahi

2010-01-01

48

Combined heterozygosity for methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C is associated with abruptio placentae but not with intrauterine growth restriction  

Microsoft Academic Search

Objective: This study was undertaken to investigate the involvement of MTHFR gene mutations C677T and A1298C implicated in vascular disease, in patients with abruptio placentae and intrauterine growth restriction (IUGR). Study Design: DNA was extracted from blood samples of 54 patients with placental vasculopathy (18 patients with abruptio placentae and 36 with IUGR) and 114 control patients and amplified by

Gabriël S. Gebhardt; Charlotte L. Scholtz; Renate Hillermann; Hein J. Odendaal

2001-01-01

49

Genotypes of the C677T and A1298C polymorphisms of the MTHFR gene as a cause of human spontaneous embryo loss  

Microsoft Academic Search

BACKGROUND: Polymorphisms C677T and A1298C of the MTHFR gene have been implicated in fetal viability. In this study, we determined the allele and genotype frequencies of these polymorphisms in different populations, includ- ing spontaneous abortion (SA) fetal tissues, with the objective of evaluating their impact on fetal viability. METHODS: 342 samples of fetal tissues, selected from SA occurring during the

G. Callejon; A. Mayor-Olea; A. J. Jimenez; M. J. Gaitan; A. R. Palomares; F. Martinez; M. Ruiz; Armando Reyes-Engel

2007-01-01

50

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C  

Microsoft Academic Search

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both

Ali Sazci; Emel Ergul; Nese Tuncer; Gurler Akpinar; Ihsan Kara

2006-01-01

51

Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: Association is significant in men but not in women  

Microsoft Academic Search

Schizophrenia is a complex and common psychiatric disorder with a polygenic inheritance. In our previous report, we showed an association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and schizophrenia in patients from Bakirkoy in Istanbul, Turkey [Sazci, A., Ergul, E., Guzelhan, Y., Kaya, G., Kara, I., 2003. Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Mol. Brain

Ali Sazci; Emel Ergul; Ismail Kucukali; Ihsan Kara; Guner Kaya

2005-01-01

52

Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients  

Microsoft Academic Search

Background: Dysfunctions in the folate metabolism can result in DNA hypom- ethylation and abnormal chromosome segregation. Two common polymor- phisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are confl icting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in

Kelly Cristina de Oliveira; Bianca Bianco; Ieda T. N. Verreschi; Alexis Dourado Guedes; Bianca Borsato Galera; Marcial Francis Galera; Caio P. Barbosa; Monica Vannucci Nunes Lipay

2008-01-01

53

MTHFR C677T and A1298C polymorphisms and cervical carcinoma susceptibility: meta-analyses based on 4,421 individuals.  

PubMed

MTHFR polymorphisms have been implicated as risk factors for several cancers. Studies have conducted on the associations of MTHFR polymorphisms with cervical carcinoma risk and have generated inconclusive results. The aim of the present study was to increase power demonstrating the possible relations. Meta-analyses examining the association between MTHFR C677T and A1298C polymorphisms and cervical carcinoma risk were performed. Separate analyses on ethnicity and source of controls were also implemented. Eligible studies were identified for the period up to Dec 2011. Eleven case-control studies containing 1859 cases and 2562 controls regarding MTHFR C677T polymorphisms were selected, of which four studies containing 461 cases and 832 controls described A1298C polymorphisms. For the overall data, no associations of MTHFR C677T polymorphisms with cervical carcinoma were observed (TT vs CC: OR = 1.07; 95 %CI = 0.73-1.58; dominant model: OR = 0.89; 95 %CI = 0.66-1.18; recessive model: OR = 1.13; 95 %CI = 0.84-1.52). In the subgroup analysis by ethnicity, MTHFR 677T allele was associated with decreased cervical cancer susceptibility among Caucasians (TT vs CC: OR = 0.65; 95 %CI = 0.45-0.93; dominant model: OR = 0.70; 95 %CI = 0.58-0.86) but not Asians. As for A1298C polymorphism, no marked associations of A1298C genetic variation with cervical cancer risk were observed (CC vs AA: OR = 1.01; 95 %CI = 0.60-1.73; dominant model: OR = 1.17; 95 %CI = 0.91-1.49; recessive model: OR = 0.99; 95 %CI = 0.60-1.63). Collectively, the results of the present study suggest that MTHFR 677T allele might play a preventive role for cervical carcinoma among Caucasians. A1298C polymorphisms might exert little effect on cervical cancerigenesis. PMID:22711309

Zhuo, Wen-Lei; Zhang, Liang; Ling, Jun-Jun; Zhu, Yi; Chen, Zheng-Tang

2012-06-19

54

Methylenetetrahydrofolate Reductase C677T and A1298C Mutations in Women with Recurrent Spontaneous Abortions in the Northwest of Iran  

PubMed Central

Introduction. Recurrent spontaneous abortion (RSA) is a significant obstetrical complication that may occur during pregnancy. Various studies in recent years have indicated that two common mutations (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene are risk factor for RSA. This study was carried out to determine the influence of (C677T and A1298C) of the methylenetetrahydrofolate reductase (MTHFR) gene mutations with RSA. Materials and Methods. A total of 139 women were included in this study: 89 women with two or more consecutive miscarriages and 50 healthy controls. Total genomic DNA was isolated from blood leukocytes. To determine the frequency of the two common C677T and A1298C MTHFR gene mutations in the patients and controls, we used two methods, amplification refractory mutation system-PCR and PCR-restriction fragment length polymorphism. Results. There is no significant difference in the prevalence of 677T/T genotype among women with RSA and healthy controls (P = 0.285). Also no statistically significant difference in the frequency of A1298C MTHFR gene mutation was detected between the two groups (P = 0.175 ). Conclusion. In conclusion, the results indicate that the Amplification Refractory Mutation System-PCR method was in complete concordance with the results obtained by standard PCR-restriction fragment length polymorphism method. The results also show no significant difference in MTHFR C677T/A1298C genotype distribution among the two groups; therefore, further studies on larger population and other genetic variants to better understand the pathobiology of RSA are needed.

Poursadegh Zonouzi, Ahmad; Chaparzadeh, Nader; Asghari Estiar, Mehrdad; Mehrzad Sadaghiani, Mahzad; Farzadi, Laya; Ghasemzadeh, Alieh; Sakhinia, Masoud; Sakhinia, Ebrahim

2012-01-01

55

B-vitamin intake, metabolic genes, and colorectal cancer risk (United States)  

Microsoft Academic Search

Objective: This population-based case–control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFR C677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC). Methods: We interviewed 727 CRC cases of Japanese, Caucasian, or Native Hawaiian origin and 727 controls matched on sex, age, and

Loïc Le Marchand; Timothy Donlon; Jean H. Hankin; Laurence N. Kolonel; Lynne R. Wilkens; Ann Seifried

2002-01-01

56

Folate pathway genetic polymorphisms and susceptibility of central nervous system tumors in Thai children  

Microsoft Academic Search

Background: Folate is an important micronutrient molecule participating in DNA synthesis, methylation and repair mechanisms. Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. The aim of

Nongnuch Sirachainan; Siranee Wongruangsri; Saowanee Kajanachumpol; Samart Pakakasama; Anannit Visudtibhan; Issarang Nuchprayoon; Apasri Lusawat; Suchart Phudhicharoenrat; Shanop Shuangshoti; Suradej Hongeng

2008-01-01

57

Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma  

Microsoft Academic Search

This pilot study has compared the polymorphic genotype frequencies of methylenetetrahydrofolate reductase (MTHFR A1298C and C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS 2R\\/3R) in 113 patients with sporadic colorectal adenocarcinoma (SCA) and 188 healthy blood donors, used as matched controls.\\u000a The aim was to assess the role of these genotypes in the increased

José Luiz Miranda Guimarães; Maria de Lurdes Ayrizono; Cláudio Saddy Rodrigues Coy; Carmen Silvia Passos Lima

58

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and nonsyndromic orofacial clefts susceptibility in a southern Chinese population.  

PubMed

Nonsyndromic orofacial clefts (NSOC) are one of the most common congenital anomalies in humans. Great efforts have been taken to unravel its genetic background. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism and two of its functional polymorphisms, MTHFR C677T and MTHFR A1298C, might be associated with NSOC susceptibility. The aim of the present study was to investigate their associations with risks of NSOC in a southern Chinese population. We found that MTHFR 677 TT and 677 CT/TT were associated with increased risk of cleft lip with or without cleft palate; meanwhile, MTHFR 1298 AC and 1298 AC/CC had protective effects against cleft lip with or without cleft palate. In further stratified analysis, we found that MTHFR 677 CT contributed to elevated risk of cleft lip only, as did MTHFR 677 CT/TT. On the contrary, MTHFR 1298 AC and 1298 AC/CC appeared to be protective against cleft lip with cleft palate. These results suggested that these two polymorphisms were involved in the development of NSOC in a southern Han Chinese population. PMID:21612398

Han, Yue; Pan, Yongchu; Du, Yifei; Tong, Na; Wang, Meilin; Zhang, Zhengdong; Wan, Linzhong; Wang, Lin

2011-05-25

59

Association between 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and conotruncal heart defects.  

PubMed

Reports related some polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) to folate-dependent neural tube defects. In view of the common origin of the cells involved both in neural tube closure and heart septation, we analyzed the MTHFR C677T and A1298C polymorphisms in mothers of children with conotruncal heart defect (CD) and in their offspring to evaluate the association between the MTHFR genotype and the risk of CD. We genotyped 103 Italian mothers with CD offspring, 200 control mothers, 103 affected children and their fathers by restriction fragment length polymorphism analysis. No increased risk was observed for the prevalence of the 677TT genotype by itself in affected children and in their mothers. The combined maternal 677TT/1298AA and 677CC/1298CC genotypes have odds ratio of 1.73 and 1.85, respectively. The prevalence of 1298CC genotype in the affected children gives odds ratio of 1.90, that becomes 2.31 for the 677CC/1298CC genotype. However, none of the odds ratios was statistically significant. We observed a higher frequency of the 677T allele in Italy than in other European countries. No association has been demonstrated between the 677TT MTHFR genotype and CD. PMID:12705333

Storti, Simona; Vittorini, Simona; Iascone, Maria R; Sacchelli, Monica; Collavoli, Anita; Ripoli, Andrea; Cocchi, Guido; Biagini, Andrea; Clerico, Aldo

2003-03-01

60

Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India.  

PubMed

Elevated homocysteine is a risk factor for many complex disorders. The role of methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine makes it one of the most important candidate genes for these disorders. Considering the heterogeneity in its distribution in world populations, we screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23 Indian caste, tribal and religious population groups from five geographical regions of India and belonging to four major linguistic groups. The frequencies of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively. MTHFR homozygous genotype 677TT was absent in eight population groups and homozygous 1298CC was absent in two population groups. 677T allele was found to be highest among north Indian populations with Indo-European tongue and 1298C was high among Dravidian-speaking tribes of east India and south India. The less common mutant haplotype 677T-1298C was observed among seven population groups and overall the frequency of this haplotype was 0.008, which is similar to that of African populations. cis configuration of 677T and 1298C was 0.94%. However, we could not find any individual with four mutant alleles which supports the earlier observation that presence of more than two mutant alleles may decrease the viability of foetus and possibly be a selective disadvantage in the population. PMID:22147263

Saraswathy, Kallur Nava; Asghar, Mohammad; Samtani, Ratika; Murry, Benrithung; Mondal, Prakash Ranjan; Ghosh, Pradeep Kumar; Sachdeva, Mohinder Pal

2011-12-07

61

Neonatal and Fetal Methylenetetrahydrofolate Reductase Genetic Polymorphisms: An Examination of C677T and A1298C Mutations  

PubMed Central

Methylenetetrahydrofolate reductase (MTHFR) mutations are commonly associated with hyperhomocysteinemia, and, through their defects in homocysteine metabolism, they have been implicated as risk factors for neural tube defects and unexplained, recurrent embryo losses in early pregnancy. Folate sufficiency is thought to play an integral role in the phenotypic expression of MTHFR mutations. Samples of neonatal cord blood (n=119) and fetal tissue (n=161) were analyzed for MTHFR C677T and A1298C mutations to determine whether certain MTHFR genotype combinations were associated with decreased in utero viability. Mutation analysis revealed that all possible MTHFR genotype combinations were represented in the fetal group, demonstrating that 677T and 1298C alleles could occur in both cis and trans configurations. Combined 677CT/1298CC and 677TT/1298CC genotypes, which contain three and four mutant alleles, respectively, were not observed in the neonatal group (P=.0402). This suggests decreased viability among fetuses carrying these mutations and a possible selection disadvantage among fetuses with increased numbers of mutant MTHFR alleles. This is the first report that describes the existence of human MTHFR 677CT/1298CC and 677TT/1298CC genotypes and demonstrates their potential role in compromised fetal viability.

Isotalo, Phillip A.; Wells, George A.; Donnelly, James G.

2000-01-01

62

Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5-FU efficacy and doubling time.  

PubMed

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time. PMID:16307843

Sasaki, Shin; Watanabe, Toshiaki; Kobunai, Takashi; Nagawa, Hirokazu

2005-11-22

63

A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine\\/folate metabolism  

Microsoft Academic Search

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine\\/methionine metabolism. The most-studied\\u000a C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased\\u000a levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C)\\u000a has also been reported to lower enzyme activity.

S. Friso; D. Girelli; E. Trabetti; C. Stranieri; O. Olivieri; E. Tinazzi; N. Martinelli; G. Faccini; P. F. Pignatti; R. Corrocher

2002-01-01

64

MTHFR ( C677T and A1298C ) Polymorphisms and Risk of Sporadic Distal Colorectal Adenoma in the UK Flexible Sigmoidoscopy Screening Trial (United Kingdom)  

Microsoft Academic Search

Objective  The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps.\\u000a \\u000a \\u000a \\u000a Methods  We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control

Panagiota N. Mitrou; Mark A. Watson; Alexandre S. Loktionov; Christopher Cardwell; Marc J. Gunter; Wendy S. Atkin; Christopher P. Macklin; Tom Cecil; Timothy D. Bishop; John Primrose; Sheila A. Bingham

2006-01-01

65

Meta and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: A Huge-GSEC review  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640

Stefania Boccia; Rayjean Hung; Gualtiero Ricciardi; Francesco Gianfagna; Matthias P. A. Ebert; Jing-Yuan Fang; Chang-Ming Gao; T. Götze; Francesco Graziano; M. Lacasaña-Navarro; Dongxin Lin; L. López-Carrillo; You-Lin Qiao; Hongbing Shen; Rachael Stolzenberg-Solomon; Toshiro Takezaki; Yu-Rong Weng; Fang Fang Zhang; P. Tikka-Kleemola; Paolo Boffetta; Emanuela Taioli

2008-01-01

66

MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma  

Microsoft Academic Search

PURPOSE: To investigate the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genotypes and plasma concentrations of total homocysteine (tHcy) in Pakistani patients with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: This was a prospective case-control study. A total of 295 patients (173 POAG, 122 PCAG) and 143 age- and sex-matched controls were subdivided into two ethnic

Shazia Micheal; Raheel Qamar; Farah Akhtar; Muhammad Imran Khan; Wajid Ali Khan; Asifa Ahmed

2009-01-01

67

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip\\/palate in northern Venezuela  

Microsoft Academic Search

Non-syndromic cleft lip with or without cleft palate (nsCL\\/P) is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL\\/P patients and, in

Mehmet A. Sözen; Marie M. Tolarova; Richard A. Spritz

2009-01-01

68

Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy  

Microsoft Academic Search

Background and aims  The enzyme MTHFR plays an important role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation,\\u000a repair, and synthesis. We analyze the relationship of MTHFR C677T and A1298C polymorphisms with biological, clinicopathological, genetic and epigenetic features of tumors, and the patient\\u000a outcome after treatment with 5-FU-based chemotherapy to determine the contribution

Antonia M. Fernández-Peralta; Lydia Daimiel; Nargisse Nejda; Daniel Iglesias; Vicente Medina Arana; Juan J. González-Aguilera

2010-01-01

69

MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients  

Microsoft Academic Search

Point mutations in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were implicated in the pathogenesis of diabetic nephropathy (DN) in many ethnic groups. This study addressed the association of C677T and A1298C single nucleotide polymorphisms (SNPs) of MTHFR gene with DN in Tunisian type 2 diabetes (T2DM) patients. Study subjects comprised 93 DN patients, 267 patients with normoalbuminuria, and 400 control subjects.

Nabil Mtiraoui; Intissar Ezzidi; Molka Chaieb; Hela Marmouche; Zied Aouni; Arbi Chaieb; Touhami Mahjoub; Martine Vaxillaire; Wassim Y. Almawi

2007-01-01

70

The Common Mutations C677T and A1298C in the Human Methylenetetrahydrofolate Reductase Gene Are Associated with Hyperhomocysteinemia and Cardiovascular Disease in Hemodialysis Patients  

Microsoft Academic Search

Background: Plasma total homocysteine (tHcy) level might be an important risk factor for the development of cardiovascular disease (CVD) in dialysis patients. While both renal failure and mutations of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene may result in hyperhomocysteinemia and CVD, the distinct roles of the thermolabile MTHFR mutation at nucleotide C677T and the more recently described mutation at nucleotide A1298C

Y. S. Haviv; V. Shpichinetsky; N. Goldschmidt; I. Abou Atta; A. Ben-Yehuda; G. Friedman

2002-01-01

71

Effects of the C677T and A1298C polymorphisms of the MTHFR gene on the genetic predisposition for diabetic nephropathy  

Microsoft Academic Search

Background. Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with low folic acid intake. A recently reported second common poly- morphism, A1298C, may increase homocysteine, but only in individuals carryingthe T677 allele. This study aimed to investigate the influence

Dariusz Moczulski; Hanna Fojcik; Ewa Zukowska-Szczechowska; Ilona Szydlowska; Wladyslaw Grzeszczak

2003-01-01

72

Association of the C677T and A1298C polymorphisms in the 5,10 methylenetetrahydrofolate reductase gene in patients with migraine risk  

Microsoft Academic Search

Although controversial, diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to migraine in Turkish people. In a case-control study, we determined the prevalence of two common MTHFR polymorphisms,C677T and A1298C, in 102 migraine patients (23 migraine with aura, 70 migraine without aura and nine with tension-type headache) and compared it to that of

Ihsan Kara; Ali Sazci; Emel Ergul; Guner Kaya; Gamze Kilic

2003-01-01

73

Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B 12 levels and the extent of coronary artery disease  

Microsoft Academic Search

The question of whether mild hyperhomocysteinemia is a risk factor for coronary artery disease (CAD) has long been debated and is still unclear. We investigated whether there is a link between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms or plasma homocysteine and CAD. This is a case-control study that included 2,121 consecutive patients (cases) with angiographically proved CAD and

Klaus Kölling; Gjin Ndrepepa; Werner Koch; Siegmund Braun; Julinda Mehilli; Albert Schömig; Adnan Kastrati

2004-01-01

74

MTHFR C677T and A1298C polymorphisms were associated with bladder cancer risk and disease progression: a meta-analysis.  

PubMed

Epidemiological studies have investigated that functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the association between these single-nucleotide polymorphisms in the MTHFR gene and the susceptibility of bladder cancer (BC) was inconsistent in previous studies. The objective of this current study was to conduct an update analysis investigating the association between three polymorphisms in the MTHFR gene and the risk of BC. We performed a meta-analysis of 13 publications involving an association between BC and MTHFR gene three polymorphisms (C677T, A1298C, and G1793A). We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). On one hand, we found that the C677T polymorphism was associated with increased BC risk among Asians, however, with decreased BC risk among a mixed population. Interestingly, BC patients who carried the T-allele (TT+TC) had a higher percentage than the individuals who carried the CC genotype (OR=1.38, 95% CI=1.13-1.69, p=0.002). On the other hand, the A1298C polymorphism may increase BC risk among Asians and Africans, but played a decreased association among Europeans. Results from the current update analysis suggested that the C677T and A1298C polymorphisms in the MTHFR gene were associated with BC risk and disease progression. PMID:23578207

You, Wu; Li, Zuo; Jing, Chen; Qian-Wei, Xing; Yu-Ping, Zhang; Weng-Guang, Li; Hua-Lei, Li

2013-04-11

75

Methylenetetrahydrofolate reductase polymorphisms, C677T and A1298C, are associated with methotrexate-related toxicities in Korean patients with rheumatoid arthritis.  

PubMed

We investigated associations between the methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and methotrexate (MTX)-related toxicities in Korean patients with rheumatoid arthritis (RA) taking MTX. One hundred sixty-seven patients with RA were enrolled in a cross-sectional study and genotyped for the single-nucleotide polymorphisms C677T and A1298C in MTHFR. Alleles, genotypes, and haplotypes of the C677T and A1298C polymorphisms were not associated with specific MTX toxicities. However, among RA patients with the 1298CC genotype, the proportion who experienced at least one toxicity was significantly greater than the proportion of patients with 1298AA who did (P = 0.043). In addition, the proportion of patients with the 677C/1298A haplotype who experienced toxicity was greater than the proportion of those with 677C/1298C who did (P = 0.032, odds ratio = 2.085, 95% confidence interval 1.058-4.106). In this study, MTHFR polymorphisms were associated with MTX toxicities in Korean patients with RA. Further study for association of MTHFR polymorphisms with MTX toxicities should be needed in larger RA population. PMID:21773884

Choe, Jung-Yoon; Lee, Hwajeong; Jung, Hyun-Young; Park, Sung-Hoon; Bae, Sang-Cheol; Kim, Seong-Kyu

2011-07-21

76

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus  

Microsoft Academic Search

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.

Mehrali Rahimi; Ali Hasanvand; Zohreh Rahimi; Asad Vaisi-Raygani; Hadi Mozafari; Mansour Rezaei; Javad Zargooshi; Farid Najafi; Ebrahim Shakiba

2010-01-01

77

C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: effect on methotrexate-related toxicity in adult acute lymphoblastic leukaemia.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. Two polymorphisms, C677T and A1298C, were described leading to reduced enzyme activity. Methotrexate (MTX) is an antifolate agent of consolidation and maintenance therapy of acute lymphoblastic leukaemia (ALL). Despite its clinical success, MTX can be associated with serious toxicities resulting in treatment interruption or discontinuation, impacting disease outcome. There is evidence that MTX toxicity can be affected by polymorphisms in genes encoding for drug-metabolizing enzymes such as MTHFR. Therefore, we aimed to investigate the influence of MTHFR C677T and A1298C polymorphisms on the frequency of MTX-related toxicity, disease outcome and patients' survival. MTHFR polymorphisms were assessed in 50 adult patients with de novo ALL using real-time PCR. Patients were followed-up for the development of haematologic and/or nonhaematologic toxicity and assessment of clinical outcome. Frequency of C677T polymorphisms was 42% for TT, 24% for CT and 34% for CC; A1298C polymorphisms were 28, 6 and 66% for CC, AC and AA, respectively. MTX therapy was significantly associated with neutropaenia, hepatic and gastrointestinal toxicities, unfavourable response at day 14 of induction therapy, increased relapse and mortality rates and shorter survival in patients with 677 TT genotype than in those with CC and CT, whereas 1298 CC genotype patients had lower frequency of neutropaenia, hepatic toxicity and relapse than in those with AA and AC. Our study suggests MTHFR polymorphism as an attractive predictor of MTX-related toxicity in adult ALL, considering it a potential prognostic factor influencing disease outcome. PMID:23183238

Eissa, Deena Samir; Ahmed, Tamer Mohamed

2013-03-01

78

Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer.  

PubMed

Authors report the results of four meta-analyses of studies that examined the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and head and neck cancer (nine studies, 2076 cases and 4834 controls for C677T; four studies, 1439 cases and 3941 controls for A1298C), and lung cancer (ten studies, 5274 cases and 7435 controls for C677T; seven studies, 5098 cases and 6243 controls for A1298C). The summary odds ratio (OR) of head and neck cancer was 0.92 (95% CI: 0.76-1.11) for MTHFR 677 TT and 0.68 (95% CI: 0.37-1.26) for MTHFR 1298 CC. The OR of lung cancer was 1.22 [95% confidence interval (CI): 0.95-1.55] for MTHFR 677 TT and 1.07 (95% CI: 0.83-1.38) for MTHFR 1298 CC. Results from the meta-analysis of three studies on C677T stratified according to dietary folate intake showed an increased risk for individuals with low folate intake (OR = 1.37, 95% CI: 0.92-2.06 for head and neck and OR = 1.28, 95% CI: 0.97-1.68 for lung) versus high folate intake (OR = 0.85, 95% CI: 0.63-1.16 for head and neck, and OR = 0.94, 95% CI: 0.79-1.12 for lung). Despite the lack of formal statistical significance, these findings are consistent with the hypothesis that folate play a role in lung and head/neck carcinogenesis, and show the need to incorporate data on folate intake when interpreting results of MTHFR polymorphisms in relation to cancer risk. PMID:18789576

Boccia, Stefania; Boffetta, Paolo; Brennan, Paul; Ricciardi, Gualtiero; Gianfagna, Francesco; Matsuo, Keitaro; van Duijn, Cornelia M; Hung, Rayjean J

2008-09-11

79

Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. PMID:18162478

Boccia, Stefania; Hung, Rayjean; Ricciardi, Gualtiero; Gianfagna, Francesco; Ebert, Matthias P A; Fang, Jing-Yuan; Gao, Chang-Ming; Götze, Tobias; Graziano, Francesco; Lacasaña-Navarro, Marina; Lin, Dongxin; López-Carrillo, Lizbeth; Qiao, You-Lin; Shen, Hongbing; Stolzenberg-Solomon, Rachael; Takezaki, Toshiro; Weng, Yu-Rong; Zhang, Fang Fang; van Duijn, Cornelia M; Boffetta, Paolo; Taioli, Emanuela

2007-12-27

80

Association between MTHFR C677T and A1298C, and MTRR A66G polymorphisms and susceptibility to schizophrenia in a Syrian study cohort.  

PubMed

The folate-homocystiene metabolic pathway has been shown to be involved in the susceptibility for developing schizophrenia by several studies. In the present study we investigated the role of three common polymorphisms of the folate-homocysteine metabolic pathway in an Arab population from Syria consisting of 85 schizophrenic patients and 126 healthy controls. The studied polymorphisms included the MTHFR C677T and A1298C, and MTRR A66G, all of which result into amino acid changes, and were previously shown to yield decreased enzymatic activity and alter plasma homocysteine concentration. While MTHFR C677T and A1298C polymorphisms were not previously studied in an Arab population with respect to the susceptibility for developing schizophrenia, the MTRR A66G was not previously investigated in any population around the world. Our results indicated a strong association between MTHFR A1298C and schizophrenia. The variant C allele frequency was significantly higher in the patients group (40% vs 29.4%, OR=1.6, 95% CI (1.06-2.41), p=0.023). A statistically significant association was found for MTHFR 677TT genotype under the recessive model in the male patients subgroup (OR=2.6, 95% CI (1.04-6.5), p=0.036), and MTHFR 677CT genotype under the overdominant model in the total patients group (OR=0.52 95% CI (0.29-0.92), p=0.024). No statistically significant association was found for MTRR A66G polymorphism on an individual basis. However, a borderline association was found for the CC/GG (C677T/A66G) compound genotype (OR=2.24, 95% CI (0.97-5.15), p=0.053). Our results support the hypothesis of association between schizophrenia and folate-homocystiene metabolic pathway genes. PMID:22813657

Lajin, Bassam; Alhaj Sakur, Amir; Michati, Roula; Alachkar, Amal

2012-04-26

81

Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene  

PubMed Central

Background: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. Objective: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. Design: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. Results: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. Conclusions: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.

Berkun, Y; Levartovsky, D; Rubinow, A; Orbach, H; Aamar, S; Grenader, T; Abou, A; Mevorach, D; Friedman, G; Ben-Yehuda, A

2004-01-01

82

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses.  

PubMed

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P = 0.026), as was secondary-level education, which was associated with early (P = 0.005), late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels. PMID:16452733

Mtiraoui, N; Zammiti, W; Ghazouani, L; Braham, N Jmili; Saidi, S; Finan, R R; Almawi, W Y; Mahjoub, T

2006-02-01

83

Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis  

Microsoft Academic Search

Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed\\u000a a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls)\\u000a showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval

Yan Huang; Shizhong Han; Yao Li; Yumin Mao; Yi Xie

2007-01-01

84

Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis.  

PubMed

Many studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and risk of fractures, but the impact of MTHFR polymorphisms on fractures risk is unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between MTHFR C677T and A1298C polymorphisms and risk of fractures. We searched the PubMed, Embase and Wanfang databases for articles relating the association between MTHFR C677T and A1298C polymorphisms and risk of fractures in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the associations. Meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of any site fractures (for T vs. C, OR = 1.17, 95 % CI 1.03-1.32; for TT vs. CC, OR = 1. 31, 95 % CI 1.11-1.54; for TT vs. CT, OR = 1.22, 95 % CI 1.04-1.43; for TT vs. CT/CC, OR = 1.31, 95 % CI 1.13-1.51). Besides, MTHFR A1298C polymorphism was also associated with increased risk of any site fractures. Subgroup meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of vertebral fractures under three genetic contrast modes (for TT vs. CC, OR = 1.43, 95 % CI 1.05-1.95; for TT vs. CT, OR = 1.36, 95 % CI 1.01-1.85; for TT vs. CT/CC, OR = 1.50, 95 % CI 1.17-1.91), but there was no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures (all P values were more than 0.05). Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of vertebral fractures compared those with heterozygote genotype CT or homozygote genotype CC. There is no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures. PMID:23229495

Bai, Rui; Liu, Wanlin; Zhao, Aiqing; Zhao, Zhenqun; Jiang, Dianming

2012-12-11

85

Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia  

PubMed Central

The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).

de Deus, Dayse Maria Vasconcelos; de Lima, Elker Lene Santos; Seabra Silva, Rafaela Maria; Leite, Edinalva Pereira; Cartaxo Muniz, Maria Tereza

2012-01-01

86

Mutations C677T and A1298C of the 5,10-methylenetetrahydrofolate reductase gene and fasting plasma homocysteine levels are not associated with the increased risk of venous thromboembolic disease.  

PubMed

Mild hyperhomocysteinemia is associated with homozygosity for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) and could increase the risk of venous thromboembolic disease (VTD). Recently, the second A1298C mutation of the MTHFR gene was described. The present study aimed to analyze both mutations of the MTHFR gene and plasma homocysteine levels in subjects with VTD. The study groups comprised 146 patients with VTD and 100 healthy subjects. There were no statistical differences in carrier frequency and allelic frequency for both A1298C and C677T mutations, nor were there any differences encountered between subjects with VTD and controls in either plasma homocysteine levels or according to C677T or A1298C genotypes of MTHFR. In our VTD patients and controls, neither MTHFR 677CT/1298CC nor MTHFR 677TT/1298CC combined genotypes were observed; double heterozygotes (A1298C/C677T) were represented only in 11% of VTD patients, and in 15% of the controls. In conclusion, the polymorphisms C677T and A1298C of MTHFR and fasting plasma homocysteine levels do not seem to be significant risk factors for venous thromboembolic disease. PMID:12138370

Domagala, T B; Adamek, L; Nizankowska, E; Sanak, M; Szczeklik, A

2002-07-01

87

Cerebral venous sinus thrombosis presenting as transient ischemic attacks in a case with homozygous mutations of MTHFR A1298C and CG677T.  

PubMed

We report a case with recurrent, transient attacks of slurred speech, weakness, and numbness of the right half of the face and the right arm without seizure activity, accompanied by headache and double vision. Neurologic examination revealed bilateral papilledema and right abducens palsy. Brain magnetic resonance imaging revealed thrombosis of the dural venous sinuses and the cortical veins, with no evidence of parenchymal lesion. Homozygous mutations were found for methylenetetrahydrofolate reductase (MTHFR) A1298C and MTHFR CG677T. Anticoagulation with heparin and warfarin resulted in prompt cessation of the transient attacks, as well as the signs and symptoms of increased intracranial pressure. This report documents that, although rare, transient ischemic attacks can result from cerebral venous thrombosis. PMID:20833086

Yildiz, Ozlem Kayim; Cevik, Seyda; Cil, Gulsum; Oztoprak, Ibrahim; Bolayir, Ertugrul; Topaktas, Suat

2010-09-15

88

Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: the A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal).  

PubMed

Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between elevated levels of homocysteine and CAD. Both MTHFR polymorphisms are associated with increased fasting homocysteine (677TT and 1298AA genotypes), but only the 1298AA variant shows an increased prevalence in CAD group. Odds ratio seem to indicate that individuals with the MTHFR 1298AA genotype and the 677CT/1298AA compound genotype had a 1.6-fold increased risk for developing CAD suggesting a possible association of MTHFR polymorphisms with the risk of CAD in Madeira population. PMID:18384842

Freitas, Ana I; Mendonça, Isabel; Guerra, Graça; Brión, Maria; Reis, Roberto P; Carracedo, Angel; Brehm, António

2008-04-01

89

The Association between Two Common Mutations C677T and A1298C in Human Methylenetetrahydrofolate Reductase Gene and the Risk for Diabetic Nephropathy in Type II Diabetic Patients1  

Microsoft Academic Search

Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephropathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whose association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes

Vlad Shpichinetsky; Itamar Raz; Yechiel Friedlander; Neta Goldschmidt; Isaiah D. Wexler; Arie Ben-Yehuda; Gideon Friedman

90

MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients  

PubMed Central

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples, MTHFR CT and CT + TT were associated with increased risk for CRC incidence [odds ratio (OR) = 2.4, 95% confidence interval (95%CI) = 1.8–4.4; OR = 2.4, 95%CI = 1.6–3.6, respectively]. Double heterozygotes 677CT/1298AC and double homozygote 677TT/1298AA and 677CC/1298CC genotypes also showed a significantly increased risk of developing CRC compared with the wild-type 677CC/1298AA genotypes of the controls. Among the 151 tumors tested, 36 (23.8%) were MSI+. MSI was more common in proximal tumors (OR = 10.4; 95%CI = 3.9–27.8) and in smokers (OR = 2.9; 95%CI = 1.3–6.7). In a case–control comparison, the MTHFR 677CT + TT genotype was strongly associated with MSI (OR = 2.6; 95%CI = 1.3–5.3). Hypermethylation of mismatch repair genes was positively related with MSI incidence in these tumor series (P = 0.00). Our data suggest that the MTHFR 677CT + TT variant genotype may be a risk factor for MSI+ cancer.

Naghibalhossaini, Fakhraddin; Mokarram, Pooneh; Khalili, Islam; Vasei, Mohammad; Hosseini, Seyed Vahid; Ashktorab, Hassan; Rasti, Mozhgan; Abdollahi, Kourosh

2013-01-01

91

Association between C677T and A1298C MTHFR Gene Polymorphism and Nonsyndromic Orofacial Clefts in the Turkish Population: A Case-Parent Study.  

PubMed

Two common MTHFR gene polymorphisms (C677T and A1298C) have been implicated in the etiology of nonsyndromic cleft lip/palate (nsCL/P). To investigate the genotype association among nsCL/P in the Turkish population, 56 case-parent trios were recruited into the study. Genotype frequencies were compared to two groups of controls from the same population. A total of 46 case-parent trios were included in transmission disequilibrium test (TDT) analysis. The mothers of the study group had a higher frequency of 677TT genotype, with a three-fold increased risk of having nsCL/P offspring (odds ratio [OR]: 3.14, p=0.03). The combined 677CT/1298AC genotype was also common among these mothers (28%), but it did not reach statistical significance (OR: 2.27, p=0.07). TDT analysis for (C677T) T allele transmission did not reveal a significant association. In conclusion, mothers carrying 677TT genotype or with 677CT/1298AC combined genotype have increased risk of having nsCL/P offspring; therefore, higher periconceptional folic acid supplementation should be advised for decreasing the recurrence risk. PMID:23692788

Semiç-Jusufagiç, Aida; Bircan, R?fat; Celebiler, Ozhan; Erdim, Melike; Akarsu, Nurten; Elçio?lu, Nursel H

92

Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects.  

PubMed

Abnormal folate/homocysteine metabolism due to polymorphisms in genes involved in this pathway has been implicated as an etiologic factor in Down syndrome (DS). This case-control study aimed to evaluate the effect of maternal C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) as risk factors for the development of DS and congenital heart defects (CHD). The distribution of these genotypic variants was similar between mothers of children with DS (n = 239) and control mothers of normal children (n = 197), but the combined genotypes 677CT or TT and 1298AA increased the risk of having offspring with DS (OR = 1.99; 95% CI 1.11-3.55). The presence of the 677T allele in case mothers resulted in a 2.07-fold higher odds of CHD in the offspring (P < 0.01). Among the 57 mothers of CHD-affected children with DS who carried the MTHFR 677CT or TT genotypes and did not have periconceptional folic acid intake, we observed a 2.26-fold increased odds (95% CI 1.25-4.09) of having any CHD-affected child with DS. Our results show that MTHFR genetic polymorphisms may be involved in the etiology of DS in our population when controlling for age. We noted a borderline significant association for the C677T polymorphism (P = 0.05). Maternal 677T allele may be associated with an increased occurrence of CHD in children with DS and we anticipate that women who carry this polymorphism would benefit from periconceptional folic acid supplementation. (c) 2009 Wiley-Liss, Inc. PMID:19725133

Brandalize, Ana Paula Carneiro; Bandinelli, Eliane; dos Santos, Pollyanna Almeida; Roisenberg, Israel; Schüler-Faccini, Lavínia

2009-10-01

93

MTHFR C677T and A1298C variant genotypes and the risk of microsatellite instability among Iranian colorectal cancer patients.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway. We aimed to test the hypothesis that C677T and A1298C variants of MTHFR predispose to microsatellite instable (MSI) colorectal cancer. We determined MTHFR genotypes in 175 sporadic colorectal cancer patients and a total of 231 normal controls in Shiraz, Southern Iran. Among the genotypes found in our samples, MTHFR CT and CT+TT were associated with increased risk for CRC incidence [odds ratio (OR)=2.4, 95% confidence interval (95%CI)=1.8-4.4; OR=2.4, 95%CI=1.6-3.6, respectively]. Double heterozygotes 677CT/1298AC and double homozygote 677TT/1298AA and 677CC/1298CC genotypes also showed a significantly increased risk of developing CRC compared with the wild-type 677CC/1298AA genotypes of the controls. Among the 151 tumors tested, 36 (23.8%) were MSI+. MSI was more common in proximal tumors (OR=10.4; 95%CI=3.9-27.8) and in smokers (OR=2.9; 95%CI=1.3-6.7). In a case-control comparison, the MTHFR 677CT+TT genotype was strongly associated with MSI (OR=2.6; 95%CI=1.3-5.3). Hypermethylation of mismatch repair genes was positively related with MSI incidence in these tumor series (P=0.00). Our data suggest that the MTHFR 677CT+TT variant genotype may be a risk factor for MSI+ cancer. PMID:20193847

Naghibalhossaini, Fakhraddin; Mokarram, Pooneh; Khalili, Islam; Vasei, Mohammad; Hosseini, Seyed Vahid; Ashktorab, Hassan; Rasti, Mozhgan; Abdollahi, Kourosh

2010-03-01

94

Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk  

Microsoft Academic Search

Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T

Ana Lívia Silva Galbiatti; Lidia Maria Rebolho Batista da Silva; Mariangela Torreglosa Ruiz-Cintra; Luis Sérgio Raposo; José Victor Maníglia; Érika Cristina Pavarino; Eny Maria Goloni-Bertollo

95

C677T and A1298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease  

Microsoft Academic Search

Background: Moderately increased plasma concentra- tions of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydro- folate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia. Methods: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of

Naomi Q. Hanson; Omer Aras; Feng Yang; Michael Y. Tsai

96

Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients  

Microsoft Academic Search

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase

Bilgen Dölek; Serpil Eraslan; Sevim Ero?lu; Belgin Eroglu Kesim; Turgut Ulutin; Altan Yalç?ner; Yahya R. Laleli; Nermin Gözükirm?z?

2007-01-01

97

Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B 12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children  

Microsoft Academic Search

One of the etiologies of hyperhomocysteinemia is decreased vitamin B12. Genetic variation in the transcobalamin II gene, the transporter of vitamin B12 to the cells, may produce altered homocysteine levels. We determined transcobalamin II C776G polymorphism, homocysteine, folate and vitamin B12 levels and analyzed the interactive effect with the methylenetetrahydrofolate reductase C677T and A1298C and methionine synthase reductase A66G polymorphisms

Ana C. M. Aléssio; Nelci F. Höehr; Lúcia H. Siqueira; Sérgio P. Bydlowski; Joyce M. Annichino-Bizzacchi

2007-01-01

98

MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms.  

PubMed

Association of two key variants mapping to the MTHFR gene (C677T (rs1801133) and A1298C (rs1801131)) with response to methotrexate (MTX) remains controversial. We investigated these and other markers spanning the gene as predictors of MTX efficacy and adverse events in a UK rheumatoid arthritis (RA) patient cohort and performed a meta-analysis of the two key variants using all published data. The tagging single nucleotide polymorphisms (SNPs) were genotyped in 309 patients with well-defined outcomes to MTX treatment and 17 studies were included in the meta-analysis. No association of the SNPs tested was detected with MTX efficacy or toxicity in our UK cohort. After combining our data with previous studies by meta-analysis, the random effects pooled odds ratios (OR) for both C677T and A1298C showed no association with efficacy or toxicity for either of the SNPs (efficacy: OR=1.05 (95% confidence interval (CI) 0.83-1.32) and OR=0.81 (95% CI 0.53-1.24), respectively; toxicity: OR=1.38 (95% CI 0.90-2.12) and OR=1.19 (95% CI 0.80-1.78), respectively). The available evidence suggests that the MTHFR C677T and A1298C gene polymorphisms are not reliable predictors of response to MTX treatment in RA patients. PMID:21931346

Owen, S A; Lunt, M; Bowes, J; Hider, S L; Bruce, I N; Thomson, W; Barton, A

2011-09-20

99

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men.  

PubMed

We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings. PMID:21046286

Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

2010-10-29

100

MTR OFFICE WINGS AT WEST SIDE OF MTR HIGH BAY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR OFFICE WINGS AT WEST SIDE OF MTR HIGH BAY REACTOR BUILDING. CONTEXTUAL VIEW. CAMERA FACING NORTHEAST. FROM LEFT TO RIGHT, TRA-652 (OFFICE WING), TRA-661 (SOUTH WING EXTENSION), SECOND/THIRD FLOOR (BALCONIES) OF MTR-603, MTR HIGH-BAY. AT RIGHT EDGE OF VIEW IS REACTOR SERVICES BUILDING (TRA-635). INL NEGATIVE NO. HD46-44-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

101

Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC)  

PubMed Central

Background. Hyperhomocysteinemia is associated with increased venous thrombosis and cardiovascular disease (CVD). Mutations in the human methylenetetrahydrofolate reductase (MTHFR) gene have been associated with increased homocysteine levels and risks of CVD in various populations including those with kidney disease. Here, we evaluated the influence of MTHFR variants on progressive loss of kidney function. Methods. We analyzed 821 subjects with hypertensive nephrosclerosis from the longitudinal National Institute of Diabetes and Digestive and Kidney Diseases African-American Study of Kidney Disease and Hypertension (AASK) Trial to determine whether decline in glomerular filtration rate (GFR) over ?4.2 years was predicted by common genetic variation within MTHFR at non-synonymous positions C677T (Ala222Val) and A1298C (Glu429Ala) or by MTHFR haplotypes. The effect on GFR decline was then supported by a study of 1333 subjects from the San Diego Veterans Affairs Hypertension Cohort (VAHC), followed over ?4.5 years. Linear effect models were utilized to determine both genotype [single-nucleotide polymorphism (SNP)] and genotype (SNP)-by-time interactions. Results. In AASK, the polymorphism at A1298C predicted the rate of GFR decline: A1298/A1298 major allele homozygosity resulted in a less pronounced decline of GFR, with a significant SNP-by-time interaction. An independent follow-up study in the San Diego VAHC subjects supports that A1298/A1298 homozygotes have the greatest estimated GFR throughout the study. Haplotype analysis with C677T yielded concurring results. Conclusion. We conclude that the MTHFR-coding polymorphism at A1298C is associated with renal decline in African-Americans with hypertensive nephrosclerosis and is supported by a veteran cohort with a primary care diagnosis of hypertension. Further investigation is needed to confirm such findings and to determine what molecular mechanism may contribute to this association.

Salem, Rany M.; Lipkowitz, Michael S.; Bhatnagar, Vibha; Pandey, Braj; Schork, Nicholas J.; O'Connor, Daniel T.

2012-01-01

102

Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients.  

PubMed

Inherited gene disorders related to the hemostatic system have been documented as risk factors for thrombosis. The roles of factor V Hong Kong (FV Hong Kong), factor V Leiden (FV Leiden), factor II G20210A (FII G20210A), methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations in Turkish patients with thrombosis (270 patients) compared with healthy controls (114 subjects) were evaluated. Polymerase chain reaction-based restriction enzyme analysis was carried out to screen these mutations, and single-strand conformation analysis was established to identify variations using the primers selected for restriction enzyme analysis studies. As a result, a significant relationship was determined among FV Leiden, FII G20210A, and thrombosis. The FV Hong Kong mutation was observed in only 2 patients with pulmonary vein thrombosis who are FV Leiden/FV Hong Kong compound heterozygous for FV gene. MTHFR C677T and A1298C were equally distributed in the patient group compared with the control group. All named mutations were also identified with single-strand conformation analysis, but a new variant/polymorphism during studies was not found. Because some inherited abnormalities are associated with thromboembolic disorders, determining the mutations and gene-to-gene interactions in patients with thrombosis history has a great impact on diagnosis and treatment of these diseases. PMID:17911197

Dölek, Bilgen; Eraslan, Serpil; Ero?lu, Sevim; Kesim, Belgin Eroglu; Ulutin, Turgut; Yalçiner, Altan; Laleli, Yahya R; Gözükirmizi, Nermin

2007-10-01

103

Polymorphisms in one-carbon metabolism pathway genes and risk for bladder cancer in a Tunisian population.  

PubMed

Cigarette smoking is the most important risk factor for bladder cancer. Moreover, epidemiologic studies have implicated several genetic variations interfering with methyl group metabolisms in susceptibility for a variety of cancers. Examples of these variations can be found in genes of the folate metabolic pathway, which is crucial in the provision of methyl groups for DNA, RNA, and protein methylation, as well as in purine and pyrimidine synthesis. We conducted a case-control study to examine the relationship between the methylenetetrahydrofolate reductase (MTHFR C677 T and MTHFR A1298C), methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase, MTR A2756 G), methionine synthase reductase (5-methyltetrahydrofolate-homocysteine methyltransferase reductase, MTRR A66 G and MTRR C524 T), and thymidylate synthase (TYMS 2R-->3R and G/C) genotypes and the risk for bladder cancer in a Tunisian population. The isolated MTHFR 677 *T, MTRR 66 *G and MTRR 524 *T variants did not appear to influence bladder cancer susceptibility. The 3R *C/3R *C genotype for the TYMS gene appears to be a protective factor against bladder cancer development (P=0.0001; OR=0.12; 95% CI=0.03-0.40). However, patients heterozygous for MTHFR A1298C or MTR A2756 G genotypes have 1.62- and 2.13-fold higher risk, respectively, of developing bladder cancer. Moreover, the combined study of MTHFR 1298 *C and MTR 2756 *G variants with either or both MTRR 66GG and TYMS 3R *G/3R *G genotypes suggests a cumulative effect. Finally, this study evidenced that interaction between gene variations involved in folate metabolism and risk of bladder cancer increased dramatically among smokers. PMID:19837268

Rouissi, Kamel; Ouerhani, Slah; Oliveira, Elisabete; Marrakchi, Raja; Cherni, Lotfi; Ben Othman, Fethi; Ben Slama, Mohamed R; Sfaxi, Mohamed; Ayed, Mohsen; Chebil, Mohamed; Amorim, António; Prata, Maria João; Benammar Elgaaied, Amel

2009-11-01

104

Association of SNPs in genes involved in folate metabolism with the risk of congenital heart disease.  

PubMed

Abstract Objective: To investigate the association of 12 single nucleotide polymorphisms (SNPs) in folate metabolic genes with congenital heart disease (CHD). Methods: A total of 160 children with CHD and 188 control children were enrolled. Twelve SNPs related to folate metabolism, including CBS-C699T, DHFR-c594?+?59del19, FOLH1-T1561C, CBS-C699T, DHFR-c594?+?59del19, GSTO1-C428T, MTHFD-G878A and -G1958A, MTHFR-C677T and -A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1?+?C11108T, RFC1-G80A, TCN2-C776T and TYMS-1494del6, were genotyped by SNaPShot genotyping technology and confirmed by Sanger sequencing. Results: There were two SNPs including NFE2L2-ins1?+?C11108T and GST01-C428T and two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G), which might increase the risk of CHD, and DHFR-c594?+?59del19 might decrease the risk of CHD. The CT genotype of NFE2L2-ins1?+?C11108T, OR?=?2.15 (95% CI?=?[1.07, 4.32], p?MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) in CHD are higher than that in control, p?MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) may increase the risk of CHD. PMID:23701284

Wang, Benjing; Liu, Minjuan; Yan, Wenhua; Mao, Jun; Jiang, Dong; Li, Hong; Chen, Ying

2013-06-10

105

Impact of methionine synthase gene and methylenetetrahydrofolate reductase gene polymorphisms on the risk of sudden sensorineural hearing loss.  

PubMed

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG--7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG--3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL. PMID:16778415

Gross, Menachem; Friedman, Gideon; Eliashar, Ron; Koren-Morag, Nira; Goldschmidt, Neta; Atta, Iman Abou; Ben-Yehuda, Arie

2006-06-14

106

Detection of Thrombophilic Mutations Related to Spontaneous Abortions by a Multiplex SNaPshot Method  

PubMed Central

Spontaneous abortion is a significant clinical problem of different etiologies. Certain thrombophilia gene mutations have been associated with an increased risk of spontaneous abortion. Also, mutations in folate-related genes can lead to abnormal chromosomal segregation during meiosis which is the most common cause of spontaneous abortion. We have developed a multiplex single-base extension reaction assay that allows simultaneous analysis of 10 different mutations in thrombophilia- and folate-related genes (Factor V Leiden G1691A, Factor V H1299R, Factor II G20210A, Factor XIII V34L, PAI-I -675 4G/5G, FGB -455G/A, MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G). Using this method we have studied 232 women who had a spontaneous abortion and 209 of their male partners. Prevalence of Factor II G20210A and Factor V H1299R mutations was significantly higher in the women than in their male partners (2.4% and 0.7%, respectively [p=0.0499] for the Factor II mutation and 9.3% and 5.7%, respectively [p=0.0485] for the Factor V mutation). The prevalence of MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G mutations did not differ between the studied groups. In conclusion, we have developed a rapid, simple, reliable, and inexpensive multiplex SNaPshot method for determination of 10 thrombophilic mutations that may result in spontaneous abortions.

Madjunkova, Svetlana; Volk, Marija; Peterlin, Borut

2012-01-01

107

Genetic Variants in the Folate Pathway and the Risk of Neural Tube Defects: A Meta-Analysis of the Published Literature  

PubMed Central

Background Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996–2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association. Methods and Findings We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07–1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24–1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models. Conclusions Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

Zhang, Ti; Lou, Jiao; Zhong, Rong; Wu, Jing; Zou, Li; Sun, Yu; Lu, Xuzai; Liu, Li; Miao, Xiaoping; Xiong, Guanglian

2013-01-01

108

Stromelysin-1 5A\\/6A and eNOS T-786C Polymorphisms, MTHFR C677T and A1298C Mutations, and Cigarette-Cannabis Smoking: A Pilot, Hypothesis-Generating Study of Gene-Environment Pathophysiological Associations With Buerger’s Disease  

Microsoft Academic Search

Buerger’s disease (BD) etiologies are poorly understood. Beyond smoking cessation, medical-surgical treatments have limited success. We hypothesized that mutations associated with arterial vasospasm (stromelysin-1 5A\\/6A, eNOS T-786C) and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7 women; 20 white, 1 African-American),

Charles J. Glueck; Mofiz Haque; Magdalena Winarska; Swapna Dharashivkar; Robert N. Fontaine; Binghua Zhu; Ping Wang

2006-01-01

109

Septal localization of the Mycobacterium tuberculosis MtrB sensor kinase promotes MtrA regulon expression.  

PubMed

The mechanisms responsible for activation of the MtrAB two-component regulatory signal transduction system, which includes sensor kinase MtrB and response regulator MtrA, are unknown. Here, we show that an MtrB-GFP fusion protein localized to the cell membrane, the septa, and the poles in Mycobacterium tuberculosis and Mycobacterium smegmatis. This localization was independent of MtrB phosphorylation status but dependent upon the assembly of FtsZ, the initiator of cell division. The M. smegmatis mtrB mutant was filamentous, defective for cell division, and contained lysozyme-sensitive cell walls. The mtrB phenotype was complemented by either production of MtrB protein competent for phosphorylation or overproduction of MtrA(Y102C) and MtrA(D13A) mutant proteins exhibiting altered phosphorylation potential, indicating that either MtrB phosphorylation or MtrB independent expression of MtrA regulon genes, including those involved in cell wall processing, are necessary for regulated cell division. In partial support of this observation, we found that the essential cell wall hydrolase ripA is an MtrA target and that the expression of bona fide MtrA targets ripA, fbpB, and dnaA were compromised in the mtrB mutant and partially rescued upon MtrA(Y102C) and MtrA(D13A) overproduction. MtrB septal assembly was compromised upon FtsZ depletion and exposure of cells to mitomycin C, a DNA damaging agent, which interferes with FtsZ ring assembly. Expression of MtrA targets was also compromised under the above conditions, indicating that MtrB septal localization and MtrA regulon expression are linked. We propose that MtrB septal association is a necessary feature of MtrB activation that promotes MtrA phosphorylation and MtrA regulon expression. PMID:22610443

Plocinska, Renata; Purushotham, Gorla; Sarva, Krishna; Vadrevu, Indumathi S; Pandeeti, Emmanuel V P; Arora, Naresh; Plocinski, Przemyslaw; Madiraju, Murty V; Rajagopalan, Malini

2012-05-20

110

MTR BUILDING, TRA603. WEST SIDE OF MTR SECOND/THIRD FLOOR AND ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING, TRA-603. WEST SIDE OF MTR SECOND/THIRD FLOOR AND HIGH-BAY REACTOR FLOOR (WITH STAIRWAY FROM ROOF). CAMERA FACING EAST FROM ROOF OF TRA-604. INL NEGATIVE NO. HD46-42-3. Mike Crane, Photographer, April 2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

111

MTR plates modeling with MAIA  

SciTech Connect

MAIA is a thermo-mechanical code dedicated to the modeling of MTR fuel plates. The main physical phenomena modeled in the code are the cladding oxidation, the interaction between fuel and Al-matrix, the swelling due to fission products and the Al/fuel particles interaction. The creeping of the plate can be modeled in the mechanical calculation. MAIA has been validated on U-Mo dispersion fuel experiments such as IRIS 1 and 2 and FUTURE. The results are in rather good agreement with post-irradiation examinations. MAIA can also be used to calculate in-pile behavior of U{sub 3}Si{sub 2} plates as in the SHARE experiment irradiated in the SCK/Mol BR2 reactor. The main outputs given by MAIA throughout the irradiation are temperatures, cladding oxidation thickness, interaction thickness, volume fraction of meat constituents, swelling, displacements, strains and stresses. MAIA is originally a two-dimensional code but a three-dimensional version is currently under development. (author)

Marelle, V.; Dubois, S.; Ripert, M.; Noirot, J. [DEN/DEC, CEA Cadarache, 13108 St Paul Lez Durance (France); Lemoine, P. [DEN/DSOE, CEA Saclay, 91191 Gif sur Yvette (France)

2008-07-15

112

Complex interaction between serum folate levels and genetic polymorphisms in folate pathway genes: biomarkers of prostate cancer aggressiveness.  

PubMed

Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed. PMID:23007265

Jackson, Maria D; Tulloch-Reid, Marshall K; McFarlane-Anderson, Norma; Watson, Alexis; Seers, Vestra; Bennett, Franklyn I; Egleston, Brian; Ragin, Camille

2012-09-25

113

Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review.  

PubMed

Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested. PMID:14977639

Sharp, Linda; Little, Julian

2004-03-01

114

MTR, SOUTH FACE OF REACTOR. SPECIAL SUPPLEMENTAL SHIELDING WAS REQUIRED ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, SOUTH FACE OF REACTOR. SPECIAL SUPPLEMENTAL SHIELDING WAS REQUIRED OUTSIDE OF MTR FOR EXPERIMENTS. THE AIRCRAFT NUCLEAR PROPULSION PROJECT DOMINATED THE USE OF THIS PART OF THE MTR. INL NEGATIVE NO. 7225. Unknown Photographer, 11/28/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

115

Levels of key enzymes of methionine-homocysteine metabolism in preeclampsia.  

PubMed

Objective. To evaluate the role of key enzymes in the methionine-homocysteine metabolism (MHM) in the physiopathology of preeclampsia (PE). Methods. Plasma and placenta from pregnant women (32 controls and 16 PE patients) were analyzed after informed consent. Protein was quantified by western blot. RNA was obtained with RNA purification kit and was quantified by reverse transcritase followed by real-time PCR (RT-qPCR). Identification of the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association analysis was carried out using Fisher's exact test. Statistical analysis was performed using a Mann-Whitney test. Results. RNA expression of MTHFR and MTR was significantly higher in patients with PE as compared with controls. Protein, SAM, and SAH levels showed no significant difference between preeclamptic patients and controls. No statistical differences between controls and PE patients were observed with the different SNPs studied. Conclusion. The RNA expression of MTHFR and MTR is elevated in placentas of PE patients, highlighting a potential compensation mechanism of the methionine-homocysteine metabolism in the physiopathology of this disease. PMID:24024209

Pérez-Sepúlveda, Alejandra; España-Perrot, Pedro P; Fernández B, Ximena; Ahumada, Verónica; Bustos, Vicente; Arraztoa, José Antonio; Dobierzewska, Aneta; Figueroa-Diesel, Horacio; Rice, Gregory E; Illanes, Sebastián E

2013-08-20

116

ETR AND MTR COMPLEXES IN CONTEXT. CAMERA FACING NORTHERLY. FROM ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ETR AND MTR COMPLEXES IN CONTEXT. CAMERA FACING NORTHERLY. FROM BOTTOM TO TOP: ETR COOLING TOWER, ELECTRICAL BUILDING AND LOW-BAY SECTION OF ETR BUILDING, HEAT EXCHANGER BUILDING (WITH U SHAPED YARD), COMPRESSOR BUILDING. MTR REACTOR SERVICES BUILDING IS ATTACHED TO SOUTH WALL OF MTR. WING A IS ATTACHED TO BALCONY FLOOR OF MTR. NEAR UPPER RIGHT CORNER OF VIEW IS MTR PROCESS WATER BUILDING. WING B IS AT FAR WEST END OF COMPLEX. NEAR MAIN GATE IS GAMMA FACILITY, WITH "COLD" BUILDINGS BEYOND: RAW WATER STORAGE TANKS, STEAM PLANT, MTR COOLING TOWER PUMP HOUSE AND COOLING TOWER. INL NEGATIVE NO. 56-4101. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

117

Mycobacterium tuberculosis mtrA merodiploid strains with point mutations in the signal-receiving domain of MtrA exhibit growth defects in nutrient broth  

PubMed Central

The genetic and biochemical aspects of the essential Mycobacterium tuberculosis MtrAB two-component regulatory signal transduction (2CRS) system have not been extensively investigated. We show by bacterial two-hybrid assay that the response regulator (RR) MtrA and the sensor kinase MtrB interact. We further demonstrate that divalent metal ions [Mg(2+), Ca(2+) or both] promote MtrB kinase autophosphorylation activity, but only Mg(2+) promotes phosphotransfer to MtrA. Replacement of the conserved aspartic acid residues at positions 13 and 56 with alanine (D13A), glutamine (D56E) or asparagine (D56N) prevented MtrA phosphorylation, indicating that these residues are important for phosphorylation. The MtrAD56E and MtrAD13A proteins bound to the promoter of fbpB, the gene encoding antigen 85B protein, efficiently in the absence of phosphorylation, whereas MtrAD56N did not. We also show that M. tuberculosis mtrA merodiploids overproducing MtrAD13A, unlike cells overproducing wild-type MtrA, grow poorly in nutrient broth and show reduced expression of fbpB. These latter findings are reminiscent of a phenotype associated with MtrA overproduction during intramacrophage growth. Our results suggest that MtrAD13A behaves like a constitutively active response regulator and that further characterization of mtrA merodiploid strains will provide valuable clues to the MtrAB system.

Zayer, Maha Al; Stankowska, Dorota; Dziedzic, Renata; Sarva, Krishna; Madiraju, Murty V.; Rajagopalan, Malini

2011-01-01

118

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

PubMed

Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Our study aimed to arrive at a more accurate estimation. Therefore, we carried out a meta-analysis of 26, 17, 9, 15, 9 and 6 case-control studies on the relationship between maternal methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G, reduced folate carrier 1 A80G and cystathionine ?-synthase 844ins68 polymorphisms and the risk of having a DS offspring. The allele contrast and model-free approach were used. Results showed marginal significant associations for MTHFR C677T, overall [odds ratio (OR) = 1.28 (1.22, 1.46) and generalised odds ratio (ORG) = 1.35 (1.16, 1.57)] and in Caucasian [OR = 1.15 (1.03, 1.29) and ORG = 1.20 (1.04, 1.38)], Asian [OR = 1.68 (1.08, 2.63) and ORG = 1.74 (1.08, 2.80)] and Brazilian [OR = 1.22 (1.04, 1.43) and ORG = 1.28 (1.06, 1.55)] populations; for MTRR A66G, overall [OR = 1.22 (1.02, 1.46) and ORG = 1.31 (1.06, 1.62)]; and for RFC1 A80G, overall [OR = 1.16 (1.02, 1.31) and ORG = 1.18 (1.01, 1.37)]. MTHFR A1298C, MTR 12756G and CBS 844ins68 polymorphisms produced non-significant results. Since potential confounders could not be ruled out completely in this meta-analysis, further studies are needed to confirm these results. PMID:24068460

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

2013-09-25

119

MTR BUILDING AND BALCONY FLOORS. CAMERA FACING EASTERLY. PHOTOGRAPHER DID ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING AND BALCONY FLOORS. CAMERA FACING EASTERLY. PHOTOGRAPHER DID NOT EXPLAIN DARK CLOUD. MTR WING WILL ATTACH TO GROUND FLOOR. INL NEGATIVE NO. 1567. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

120

MTR AND ETR COMPLEXES. CAMERA FACING EASTERLY TOWARD CHEMICAL PROCESSING ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR AND ETR COMPLEXES. CAMERA FACING EASTERLY TOWARD CHEMICAL PROCESSING PLANT. MTR AND ITS ATTACHMENTS IN FOREGROUND. ETR BEYOND TO RIGHT. INL NEGATIVE NO. 56-4100. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

121

REACTIVITY MEASUREMENT FACILITY, UNDER CONSTRUCTION OVER MTR CANAL IN BASEMENT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

REACTIVITY MEASUREMENT FACILITY, UNDER CONSTRUCTION OVER MTR CANAL IN BASEMENT OF MTR BUILDING, TRA-603. WOOD PLANKS REST ON CANAL WALL OBSERVABLE IN FOREGROUND. INL NEGATIVE NO. 11745. Unknown Photographer, 8/20/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

122

PRECONSTRUCTION IMAGE OF THE MTR SITE. ABANDONED IRRIGATION CANAL (FROM ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PRE-CONSTRUCTION IMAGE OF THE MTR SITE. ABANDONED IRRIGATION CANAL (FROM EARLY 1900s) ILLUSTRATES FLATNESS OF MTR/TRA TERRAIN. FEATURE ON HORIZON IN LEFT OF VIEW IS EXPLORATORY WATER DRILLING EQUIPMENT. CAMERA LOOKS SOUTHEAST. INL NEGATIVE NO. 136. Unknown Photographer, 12/5/1949 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

123

MTR CANAL IS FILLED WITH WATER. MAN STANDS ON MOVABLE ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR CANAL IS FILLED WITH WATER. MAN STANDS ON MOVABLE BRIDGE. NOTE CHAINS AND HOOK AT LEFT. THIS SECTION OF CANAL PROJECTED EAST BEYOND THE SITE OF THE MTR BUILDING. INL NEGATIVE NO. 6003. Unknown Photographer, 6/16/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

124

CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONTEXTUAL AERIAL VIEW OF "EXCLUSION" MTR AREA WITH IDAHO CHEMICAL PROCESSING PLANT IN BACKGROUND AT CENTER TOP OF VIEW. CAMERA FACING EAST. EXCLUSION GATE HOUSE AT LEFT OF VIEW. BEYOND MTR BUILDING AND ITS WING, THE PROCESS WATER BUILDING AND WORKING RESERVOIR ARE LEFT-MOST. FAN HOUSE AND STACK ARE TO ITS RIGHT. PLUG STORAGE BUILDING IS RIGHT-MOST STRUCTURE. NOTE FAN LOFT ABOVE MTR BUILDING'S ONE-STORY WING. THIS WAS LATER CONVERTED FOR OFFICES. INL NEGATIVE NO. 3610. Unknown Photographer, 10/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

125

MTR BASEMENT. GENERAL ELECTRIC CONTROL CONSOLE FOR AIRCRAFT NUCLEAR PROPULSION ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BASEMENT. GENERAL ELECTRIC CONTROL CONSOLE FOR AIRCRAFT NUCLEAR PROPULSION EXPERIMENT NO. 1. INL NEGATIVE NO. 6510. Unknown Photographer, 9/29/1959 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

126

TOP OF MTR. CONTROL RODS AND GRID PLATE EMERGE FROM ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

TOP OF MTR. CONTROL RODS AND GRID PLATE EMERGE FROM REACTOR TANK. INL NEGATIVE NO. 6206. R.G. Larsen, Photographer, 6/27/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

127

Clinically feasible MTR is sensitive to cortical demyelination in MS  

PubMed Central

Objective: Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS. Methods: MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density–weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MMctx), mostly demyelinated (MDctx), or intermediately demyelinated (IDctx). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex. Results: We found that mean normalized cortical MTR was significantly lower in cortical tissue with any demyelination (IDctx or MDctx) compared to MMctx (demyelinated cortex: least-squares mean [LSM] = 0.797, SE = 0.007; MMctx: LSM = 0.837, SE = 0.006; p = 0.01, n = 89). Conclusions: This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS.

Chen, Jacqueline Tien-Hsiang; Easley, Kathryn; Schneider, Colleen; Nakamura, Kunio; Kidd, Grahame J.; Chang, Ansi; Staugaitis, Susan M.; Fox, Robert J.; Fisher, Elizabeth; Arnold, Douglas L.; Trapp, Bruce D.

2013-01-01

128

Direct genotyping of single nucleotide polymorphisms in methyl metabolism genes using probe-free high-resolution melting analysis.  

PubMed

High-resolution melting (HRM) shows great promise for high-throughput, rapid genotyping of individual polymorphic loci. We have developed HRM assays for genotyping single nucleotide polymorphisms (SNP) in several key genes that are involved in methyl metabolism and may directly or indirectly affect the methylation status of the DNA. The SNPs are in the 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T and A1298C), methionine synthetase (MTR; 5-methyltetrahydrofolate-homocysteine methyltransferase; A2756G), and DNA methyltransferase 3b (DNMT3b; C46359T and C31721T) loci. The choice of short amplicons led to greater melting temperature (Tm) differences between the two homozygous genotypes, which allowed accurate genotyping without the use of probes or spiking with control DNA. In the case of MTHFR, there is a second rarer SNP (rs4846051) close to the A1298C SNP that may result in inaccurate genotyping. We masked this second SNP by placing the primer over it and choosing a base at the polymorphic position that was equally mismatched to both alleles. The HRM assays were done on HRM capable real-time PCR machines rather than stand-alone HRM machines. Monitoring the amplification allows ready identification of samples that may give rise to aberrant melting curves because of PCR abnormalities. We show that samples amplifying markedly late can give rise to shifted melting curves without alteration of shapes and potentially lead to misclassification of genotypes. In conclusion, rapid and high-throughput SNP analysis can be done with probe-free HRM if sufficient attention is paid to amplicon design and quality control to omit aberrantly amplifying samples. PMID:18483346

Kristensen, Lasse S; Dobrovic, Alexander

2008-05-01

129

[Development of the high-throughput fluorescence assay detecting SNPs in hemostasis and folate metabolism genes for clinical use].  

PubMed

Genetic predisposition of an individual patient should be taken in account to choose the proper treatment. Implementation to clinical practice requires the development of rapid, high-throughput, and easy assays intended to detect single nucleotide polymorphisms. A detection kit intended to identify the hemostasis and folate cycle gene mutations G20210A FII, G1691A FV, G10976A FVII, G103T FXIII, C807T ITGA2, T1565C ITGB3, 5G(-675)4G PAI, G(-455)A FGB, C677T and A1298C MTHFR, A2756G MTR, A66G MTRR was suggested in this work. The method is based on the polymerase chain reaction and subsequent melt curve analysis of the complexes of amplicons with specific probe. Three single nucleotide polymorphisms can be identified in one tube using our detection kit that increases the productivity of the analysis in the clinical use. Different types of biological samples (buccal epithelium, saliva, plasma, serum, and urogenital swabs) can be used as the initial material for DNA isolation and further analysis by the method developed in this work. PMID:23785789

Prasolova, M A; Shchepotina, E G; Dymshits, G M

2013-01-01

130

Polymorphisms in Methionine Synthase, Methionine Synthase Reductase and Serine Hydroxymethyltransferase, Folate and Alcohol Intake, and Colon Cancer Risk  

PubMed Central

Background/Aims We examined associations among folate and alcohol intake, SNPs in genes involved in one-carbon metabolism and colon cancer risk. Methods Colon cancer cases (294 African Americans and 349 whites) were frequency matched to population controls (437 African Americans and 611 whites) by age, race and sex from 33 North Carolina counties from 1996 to 2000. Folate and alcohol intakes were collected by dietary interview. Five SNPs were genotyped using DNA from whole blood: SHMT C1420T; MTRR A66G; MTR A2756G, and the previously-reported MTHFR C677T and MTHFR A1298C. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Results An inverse association was observed for SHMT TT genotype as compared to CC genotype in whites (OR=0.6, 95%CI=0.4, 1.0), but not in African Americans. Inverse associations were observed for high folate intake in individuals carrying 0 or 1 variant allele [OR 0.2 (95%CI 0.06 – 0.8) for African Americans; OR 0.2 (95%CI 0.1– 0.6) for whites] compared to low folate intake. Modest interactions between these SNPs and alcohol or folate intakes were observed. Conclusions Our results are consistent with other findings and provide needed data on these associations among African Americans.

Steck, Susan E.; Keku, Temitope; Butler, Lesley M.; Galanko, Joseph; Massa, Beri; Millikan, Robert C.; Sandler, Robert S.

2009-01-01

131

Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women  

PubMed Central

Background Several studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated. Methods A case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12 were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR A2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Neither dietary intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23–3.83; Ptrend = 0.010). The MTR 2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01–3.92; Ptrend = 0.801), and statistically significant interactions with regard to risk were observed between the MTHFR A1298C polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022). Conclusion MTHFR polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12 had no overall association with breast cancer risk. However, increased risk was observed in total women with the MTR 2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions between MTHFR polymorphisms and B vitamins, warrant further investigation.

2009-01-01

132

Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent.  

PubMed

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case-control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ?50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms. PMID:22134752

Carvalho Barbosa, Rita de Cássia; Menezes, Débora Costa; Freire, Thiago Fernando Vasconcelos; Sales, Diogo Campos; Alencar, Victor Hugo Medeiros; Rabenhorst, Silvia Helena Barem

2011-12-02

133

MTR COMPRESSOR BUILDING, TRA651. RELATED AIR COMPRESSOR EQUIPMENT OUTSIDE BUILDING. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR COMPRESSOR BUILDING, TRA-651. RELATED AIR COMPRESSOR EQUIPMENT OUTSIDE BUILDING. PIPE LEADS BELOW GRADE INTO MTR BUILDING. CAMERA FACING WEST, IE, EAST SIDE OF MTR BUILDING. INL NEGATIVE NO. 56-1265. Jack L. Larsen, Photographer, 4/20/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

134

Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population  

Microsoft Academic Search

BackgroundHyperhomocysteinemia (>15 µmol\\/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-?-synthase (CBS; T833C\\/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a

Mohsin Yakub; Naushad Moti; Siddiqa Parveen; Bushra Chaudhry; Iqbal Azam; Mohammad Perwaiz Iqbal

2012-01-01

135

Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis  

Microsoft Academic Search

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis\\u000a by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case–control study of 239 bladder cancer cases and\\u000a 250 cancer-free controls, we found that the MTHFR 677TT

Meilin Wang; Haixia Zhu; Guangbo Fu; Miaomiao Wang; Zhizhong Zhang; Qiang Lu; Shizhi Wang; Zhengdong Zhang

2009-01-01

136

MTR COOLING TOWER. BASIN IS ADJACENT TO PUMP HOUSE. CAMERA ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR COOLING TOWER. BASIN IS ADJACENT TO PUMP HOUSE. CAMERA FACES SOUTHEAST TOWARD NORTH SIDE OF PUMP HOUSE. INL NEGATIVE NO. 2690. Unknown Photographer, 6/1951. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

137

CAMERA IS ON CATWALK ABOVE MTR. CRANE HOOK LOWERS TOP ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CAMERA IS ON CATWALK ABOVE MTR. CRANE HOOK LOWERS TOP PLUG ONTO REACTOR. NOTE PLANK-LIKE BRIDGE (WALKWAY) TO BALCONY AT UPPER RIGHT. INL NEGATIVE NO. 4502. Unknown Photographer, probable date 3/31/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

138

REACTIVITY MEASUREMENT FACILITY. CAMERA LOOKS DOWN INTO MTR CANAL. REACTOR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

REACTIVITY MEASUREMENT FACILITY. CAMERA LOOKS DOWN INTO MTR CANAL. REACTOR IS FUELED AS AN ETR MOCK-UP. LIGHTS DANGLE BELOW WATER LEVEL. CONTROL RODS AND OTHER APPARATUS DESCEND FROM ABOVE WATER LEVEL. INL NEGATIVE NO. 56-900. Jack L. Anderson, Photographer, 3/26/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

139

Harmonic simulation of MTR traction system by EMTP  

Microsoft Academic Search

The proliferation of nonlinear loads resulting from new technologies has increased the levels of harmonics in power systems, and traction systems represent large nonlinear loads. This paper presents results of a simulation and site measurement study of the harmonics related to Mass Transit Railway (MTR) in Hong Kong. Simulation results from the ATP Electromagnetic Transient Program (EMTP) are compared with

Laurence Snider; Edward Lo; Terrance Lai

1999-01-01

140

MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR CONTROL ROOM WITH CONTROL CONSOLE AND STATUS READOUTS ALONG WALL. WORKERS MAKE ELECTRICAL AND OTHER CONNECTIONS. INL NEGATIVE NO. 4289. Unknown Photographer, 2/26/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

141

CUTS FOR MTR EXCAVATION ILLUSTRATE SEDIMENTARY MANTLE OF SOIL AND ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CUTS FOR MTR EXCAVATION ILLUSTRATE SEDIMENTARY MANTLE OF SOIL AND GRAVEL OVERLAYING LAVA ROCK FIFTY FEET BELOW. SAGEBRUSH HAS BEEN SCOURED FROM REST OF SITE. CAMERA PROBABLY FACES SOUTHWEST. INL NEGATIVE NO. 67. Unknown Photographer, 6/4/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

142

Electrochemical Characterization Shewanella oneidensis () Mr-1 MtrABC  

NASA Astrophysics Data System (ADS)

Dissimilatory iron-reducing bacteria have the ability to use a wide range of terminal electron acceptors including solid state iron (oxihydr)oxides. It is generally accepted that electrons are transferred by electron transfer proteins to a series of multiheme c-type cytochromes which enable the electron transport from the periplasm to the extracellular side of the outer cell membrane and across the bacteria-mineral interface to the terminal electron acceptor. In the last decade, the facultative anaerobe organism Shewanella oneidensis Mr-1 has been used as a model organism to identify, purify, and sequence single proteins involved in Fe(III) and Mn(IV) reduction, but these studies have provided little biochemical information on the actual electron transfer process within the bacterial cell. In order to extend the knowledge on electron transfer, Ross et al.(in press) have recently purified a complex from Shewanella oneidensis Mr-1 which includes the membrane proteins MtrA, MtrB, and MtrC and spans the space from the periplasm to the extracellular side of the outer membrane. In our study we applied the relatively new technique of protein film electrochemistry to the MtrABC complex to gain more biochemical information on electron transport in the membrane of Shewanella oneidensis Mr-1. A wealth of information on the reaction of redox-active sites in proteins like MtrABC can be acquired by voltammetric studies in which the protein sample is immobilized as a layer onto an electrode surface. By carrying out cyclic voltammetry over a wide range of scan rates, the data can be analyzed in terms of peak potentials versus scan rate. A simple reversible electron transfer process gives rise to a trumpet-shaped plot because the oxidation and the reduction peaks increasingly separate at high scan rate. In this contribution we show a detailed electrochemical picture of the MtrABC complex, which gives insight into the electron transfer from the periplasm to the extracellular side of the outer membrane of Shewanella oneidensis Mr-1. Such electrochemical analysis will help to understand how electrons are transferred to solid state electron acceptors such as ferrihydrite or goethite with different mineralogical and thermodynamic properties. Ross, D. E., Ruebush, S. S., Brantley, S. L., Hartshorne, R. S., Clarke, T. A., Richardson, D. J., and Tien, M., in press. Characterization of Protein/Protein Interactions Involved in Iron Reduction by Shewanella oneidensis MR-1. Applied and Environmental Microbiology.

Nuester, J.; Ross, D. E.; Hartshorne, R. S.; Brantley, S. L.; Butt, J. N.; Richardson, D.; Tien, M.

2007-12-01

143

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer  

PubMed Central

Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

Zhou, Daijun; Mei, Qiang; Luo, Han; Tang, Bo; Yu, Peiwu

2012-01-01

144

MTR MAIN FLOOR. NEUTRON TUNNEL (SPANNED BY STILELIKE STEPS) PROJECTS ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR MAIN FLOOR. NEUTRON TUNNEL (SPANNED BY STILE-LIKE STEPS) PROJECTS FROM THE SOUTHEAST CORNER OF THE MTR TOWARD SOUTHEAST CORNER OF BUILDING, WHERE SHIELDING BLOCKS BEGIN TO SURROUND THE TUNNEL AS IT NEARS DETECTING INSTRUMENTS NEAR THE BUILDING WALL. GEAR RELATED TO CRYSTAL NEUTRON SPECTROMETER IS IN FOREGROUND SURROUNDED BY SHIELDING. DATA CONSOLES ARE AT MID-LEVEL OF EAST FACE. OTHER WORK PROCEEDS ON TOP OF AND ELSEWHERE AROUND REACTOR. NOTE TOOLS HANGING AGAINST SOUTHEAST CORNER, USED TO CHANGE FUEL ELEMENTS AND OTHER REACTOR ITEMS DURING REFUELING CYCLES. INL NEGATIVE NO. 10439. Unknown Photographer, 4/20/1954 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

145

MTR BASEMENT. DOORWAY TO SOURCE STORAGE VAULT IS AT CENTER ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BASEMENT. DOORWAY TO SOURCE STORAGE VAULT IS AT CENTER OF VIEW; TO DECONTAMINATION ROOM, AT RIGHT. PART OF MAZE ENTRY IS VISIBLE INSIDE VAULT DOORWAY. INL NEGATIVE NO. 7763. Unknown Photographer, photo was dated as 3/30/1953, but this was probably an error. The more likely date is 3/30/1952. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

146

CONTROL CONSOLE FOR MTR FISSION PRODUCT MONITOR, USED TO DETECT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONTROL CONSOLE FOR MTR FISSION PRODUCT MONITOR, USED TO DETECT BREAKS IN CLADDING OF FUEL ELEMENTS. COUNT-RATE METER IN TOP PANEL INDICATES AMOUNT OF RADIOACTIVITY. LOWER PANELS SUPPLY POWER AND AMPLIFICATION OF SIGNALS GENERATED BY SCINTILLATION COUNTER/PHOTOMULTIPLIER TUBE COMBINATION IN RESPONSE TO RADIOACTIVITY IN A SAMPLE OF THE COOLING WATER. INL NEGATIVE NO. 56-771. Jack L. Anderson, Photographer, 3/15/1956. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

147

VALIDATION AND VERIFICATION OF THE MTR_PC THERMOHYDRAULIC PACKAGE  

Microsoft Academic Search

The MTR_PC v2.6 is a computational package developed for research reactor design and calculation. It covers three of the main aspects of a research reactor: neutronic, shielding and thermohydraulic. In this work only the thermohydraulic package will be covered, dealing with verification and validation aspects. The package consists of the following steady state programs: CAUDVAP 2.60 for the hydraulic calculus,

Alicia Doval

148

Gamma-ray spectroscopy on irradiated MTR fuel elements  

Microsoft Academic Search

The availability of burnup data is an important requirement in any systematic approach to the enhancement of safety, economics and performance of a nuclear research reactor. This work presents the theory and experimental techniques applied to determine, by means of nondestructive gamma-ray spectroscopy, the burnup of Material Testing Reactor (MTR) fuel elements irradiated in the IEA-R1 research reactor. Burnup measurements,

L. A. A Terremoto; C. A Zeituni; J. A Perrotta; J. E. R da Silva

2000-01-01

149

TOP OF MTR. MAN CLIMBS FRAME ON FOOT LADDER TO ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

TOP OF MTR. MAN CLIMBS FRAME ON FOOT LADDER TO POSITION CRANE HOOK, WHICH WILL LIFT TOP PLUG FROM REACTOR AS A STEP IN REFUELING PROCEDURES. NOTE CRANE OPERATOR AT UPPER LEFT OF VIEW. ENTIRE APPARATUS, INCLUDING FRAME AND DRIVES FOR CONTROL RODS, WILL BE LIFTED. INL NEGATIVE NO. 6199. R.G. Larsen, Photographer, 6/22/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

150

TEST REACTOR AREA PLOT PLAN CA. 1968. MTR AND ETR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

TEST REACTOR AREA PLOT PLAN CA. 1968. MTR AND ETR AREAS SOUTH OF PERCH AVENUE. "COLD" SERVICES NORTH OF PERCH. ADVANCED TEST REACTOR IN NEW SECTION WEST OF COLD SERVICES SECTION. NEW PERIMETER FENCE ENCLOSES BETA RAY SPECTROMETER, TRA-669, AN ATR SUPPORT FACILITY, AND ATR STACK. UTM LOCATORS HAVE BEEN DELETED. IDAHO NUCLEAR CORPORATION, FROM A BLAW-KNOX DRAWING, 3/1968. INL INDEX NO. 530-0100-00-400-011646, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

151

WORKERS FABRICATE ROOF SLABS FOR MTR BUILDING AT THE CONSTRUCTION ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WORKERS FABRICATE ROOF SLABS FOR MTR BUILDING AT THE CONSTRUCTION SITE. FORMS WERE MADE OF STEEL. AFTER AN INCH OF CONCRETE HAD BEEN POURED IN THE FORM, A MAT OF REINFORCING STEEL WAS PLACED ON IT. THE REMAINDER OF THE FORM WAS FILLED, AND THE CONCRETE WAS VIBRATED, STRUCK, AND TROWELED. GROOVES AT CORNER WILL HAVE 1/4 INCH RODS WELDED INTO THE EYE OF THE STEEL MAT FOR GROUNDING. INL NEGATIVE NO. 578. Unknown Photographer, 9/1/1950 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

152

Thermal–hydraulic modeling of the onset of flow instability in MTR reactors  

Microsoft Academic Search

Prediction of the onset of the flow instability (OFI) in steady and transient sub-cooled flow boiling is an important consideration in the design and operation of nuclear reactors, in particular for materials testing reactors (MTR). In this study, a predictive model for OFI in the MTR has been developed. The model is based on both the heat balance during the

Hany A. Khater; Salah El-Din El-Morshedy; Mohamed M. A. Ibrahim

2007-01-01

153

MTR, TRA603. SOURCE STORAGE VAULT IN BASEMENT. MAZE ENTRY. SOLID ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. SOURCE STORAGE VAULT IN BASEMENT. MAZE ENTRY. SOLID CONCRETE WALLS. CONCRETE PLUGS, ONE LINED WITH LEAD, AND LIFT HANDLES. FLOOR WELLS SIX FEET DEEP BELOW FLOOR. IDO MTR-603-IDO-5, 12/1952. INL INDEX NO. 531-0603-00-396-110469, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

154

Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk.  

PubMed

Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age ? 49 years (P<0.001), male gender (P=0.03), tobacco habit (P<0.001), MTHFR 1298AC/CC (P=0.028), MTR 2756AG/GG (P=0.010) and RFC1 80AG/GG (P=0.015) genotypes were associated with an increased risk of HNSCC. There were interactions between lower survival and CBS 844ins68 (P=0.005); age ? 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P=0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. PMID:22051736

Galbiatti, Ana Lívia Silva; da Silva, Lidia Maria Rebolho Batista; Ruiz-Cintra, Mariangela Torreglosa; Raposo, Luis Sérgio; Maníglia, José Victor; Pavarino, Erika Cristina; Goloni-Bertollo, Eny Maria

2011-11-01

155

Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma.  

PubMed

This pilot study has compared the polymorphic genotype frequencies of methylenetetrahydrofolate reductase (MTHFR A1298C and C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS 2R/3R) in 113 patients with sporadic colorectal adenocarcinoma (SCA) and 188 healthy blood donors, used as matched controls. The aim was to assess the role of these genotypes in the increased risk of SCA among the southeastern Brazilian population. Carriers of genotype MTRR 66GG, or the combined variants MTHFR 1298AC?+?CC plus 677CT?+?TT, or MTHFR 677CT?+?TT plus MTR 2756AG?+?GG, or MTHFR 1298AC?+?CC plus 677CT?+?TT plus MTR 2756AG?+?GG, or yet, MTHFR 1298AC?+?CC plus 677CT?+?TT plus MTRR 66AG?+?GG, respectively, showed an increased risk of the order of 1.99-, 3.26-, 2.22-, 10.92-, and 14.88-fold of developing SCA when compared with carriers of the other studied polymorphic genotypes, whether in isolation or in combination. In addition, individuals with the MTHFR 677CT?+?TT or the MTR 2756AG?+?GG genotypes had a 2.12- and a 1.42-fold increased risks of SCA onset before 50 years of age. African-Brazilians with the MTRR 66GG genotype had a 1.98-fold increased risk of SCA while individuals with the MTR 2756AG?+?GG and the MTHFR 677CT?+?TT genotypes showed a 2.11- and a 1.62-fold increased risk of undifferentiated and advanced tumors at diagnosis, respectively. Carriers of genotype MTHFR 1298AC?+?CC or MTHFR 1298AC?+?CC plus MTRR 66AG?+?GG had a 1.42- and a 3.07-fold increased risk of rectal tumor, respectively. Additionally, carriers of MTHFR 677CT?+?TT or MTHFR 677CT?+?TT plus TS 2R/3R?+?3R/3R had a 1.55- and a 5.39-fold increased risk for colon tumor, respectively, in comparison with carriers of the wild genotypes. These data suggest that all polymorphisms coding for folate and methionine-dependent enzymes, particularly when present in combination with other polymorphisms, have consistent roles in the increased risk of SCA among the southeastern population of Brazil. PMID:21603981

Guimarães, José Luiz Miranda; Ayrizono, Maria de Lurdes; Coy, Cláudio Saddy Rodrigues; Lima, Carmen Silvia Passos

2011-05-21

156

CONTEXTUAL AERIAL VIEW OF "COLD" NORTH HALF OF MTR COMPLEX. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONTEXTUAL AERIAL VIEW OF "COLD" NORTH HALF OF MTR COMPLEX. CAMERA FACING EASTERLY. FOREGROUND CORNER CONTAINS OIL STORAGE TANKS. WATER TANKS AND WELL HOUSES ARE BEYOND THEM TO THE LEFT. LARGE LIGHT-COLORED BUILDING IN CENTER OF VIEW IS STEAM PLANT. DEMINERALIZER AND WATER STORAGE TANK ARE BEYOND. SIX-CELL COOLING TOWER AND ITS PUMP HOUSE ARE ABOVE IT IN VIEW. SERVICE BUILDINGS INCLUDING CANTEEN ARE ON NORTH SIDE OF ROAD. "EXCLUSION" AREA IS BEYOND ROAD. COMPARE LOCATION OF EXCLUSION-AREA GATE WITH PHOTO ID-33-G-202. INL NEGATIVE NO. 3608. Unknown Photographer, 10/30/1951 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

157

Relationship between mutation of IR in the mtr system of neisseria gonorrhoeae and multiple antibiotic resistance  

Microsoft Academic Search

Summary  To study the relationship between mutation of the inverted repeat sequence (IR) in the multiple transferable resistant system\\u000a (mtr) of Neisseria gonorrhoeae (NG) and its multiple antibiotic resistance, minimal inhibitory concentrations (MICs) for the\\u000a clinically isolated strains were tested by agar-dilution-method. The mtr systems IR gene of NG was sequenced after amplification\\u000a by polymerase chain reaction (PCR). Either two susceptive

Zhang Lixia; Lin Nengxing; Huang Changzheng; Chen Hongxiang; Lin Yun; TU Yating

2006-01-01

158

MTR, TRA603. THIRD FLOOR PLAN AND ROOF PLAN. CONTROL ROOM, ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. THIRD FLOOR PLAN AND ROOF PLAN. CONTROL ROOM, OFFICES, CONFERENCE ROOM, BATHROOMS. HOOD VENT. BALCONY CONNECTS THIRD FLOOR TO AND SIDES OF MTR. STAIRWAYS TO BALCONY PLATFORMS AROUND REACTOR. CRANE ACCESS CATWALK. BLAW-KNOX 3150-803-4, 7/1950. INL INDEX NO. 531-0603-00-098-100563, REV. 10. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

159

PUMP HOUSE FOR MTR WELL NO. 1, TRA601. FLOOR PLAN, ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PUMP HOUSE FOR MTR WELL NO. 1, TRA-601. FLOOR PLAN, ELEVATIONS, SECTION SHOWING WELL CASING, ROOF FRAMING PLAN. AS BUILT. WELL HOUSE FOR WELL NO. 2, TRA-602, WAS IDENTICAL IN ALL PARTICULARS EXCEPT FLOOR DIMENSIONS AND ARRANGEMENT OF PUMP AND ELECTRICAL EQUIPMENT INSIDE. IDAHO OPERATIONS OFFICE MTR-601-IDO-1, 12/1954. INL INDEX NO. 531-0601-00-396-110463, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

160

Nuclear mRNA accumulation causes nucleolar fragmentation in yeast mtr2 mutant.  

PubMed Central

We have identified a set of genes that affect mRNA transport (mtr) from the nucleus to the cytoplasm of Saccharomyces cerevisiae. One of these genes, MTR2, has been cloned and shown to encode a novel 21-kDa nuclear protein that is essential for vegetative growth. MTR2 shows limited homology to a protein implicated in plasmid DNA transfer in Escherichia coli. PolyA+RNA accumulates within the nucleus of mtr2-1 in two to three foci at 37 degrees C. mRNA, tRNA, and rRNA synthesis continue as do pre-mRNA splicing, tRNA processing, and rRNA export at 37 degrees C. Under these conditions the polyA tail length increases, and protein synthesis is progressively inhibited. Nucleolar antigens also redistribute to two to three nuclear foci at 37 degrees C, and this redistribution depends on ongoing transcription by RNA polymerase II. Surprisingly, these foci coincide with the sites of polyA+RNA accumulation. Comparable colocalization and dependance on RNA polymerase II transcription is seen for the mtr1-1 mutant. The disorganization of the nucleolus thus depends on mRNA accumulation in these mutants. We discuss the possible functions of MTR2 and the yeast nucleolus in mRNA export. Images

Kadowaki, T; Hitomi, M; Chen, S; Tartakoff, A M

1994-01-01

161

Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population  

Microsoft Academic Search

An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and\\/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)—a critical nutritional factor, deficiency of which results in hyperhomocysteinemia. Hence, polymorphisms in

Jitender Kumar; Swapan K. Das; Priyanka Sharma; Ganesan Karthikeyan; Lakshmy Ramakrishnan; Shantanu Sengupta

2005-01-01

162

A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis  

Microsoft Academic Search

INTRODUCTION: We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients

Rogelio Palomino-Morales; Carlos Gonzalez-Juanatey; Tomas R Vazquez-Rodriguez; Luis Rodriguez; Jose A Miranda-Filloy; Benjamin Fernandez-Gutierrez; Javier Llorca; Javier Martin; Miguel A Gonzalez-Gay

2010-01-01

163

A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis  

PubMed Central

Introduction We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA. Methods Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo and Hospital San Carlos, Madrid, were studied. Patients and controls (n = 865) were genotyped using predesigned TaqMan SNP genotyping assays. Results No significant differences in allele or genotype frequencies for the MTHFR gene polymorphisms between RA patients and controls were found. Also, no association between the MTHFR 677 C>T polymorphism and CV events or endothelial dysfunction was observed. However, the MTHFR 1298 allele C frequency was increased in patients with CV events after 5 years (38.7% versus 30.3%; odds ratio = 1.45; 95% confidence interval = 1.00 to 2.10; P = 0.04) and 10 years (42.2% versus 31.0%; odds ratio = 1.62; 95% confidence interval = 1.08 to 2.43; P = 0.01) follow up. Moreover, patients carrying the MTHFR 1298 AC and CC genotypes had a significantly decreased flow-mediated endothelium-dependent vasodilatation (4.3 ± 3.9%) compared with those carrying the MTHFR 1298 AA genotype (6.5 ± 4.4%) (P = 0.005). Conclusions Our results show that the MTHFR 1298 A>C gene polymorphism confers an increased risk for subclinical atherosclerosis and CV events in patients with RA.

2010-01-01

164

Mtr Extracellular Electron Transfer Pathways in Fe(III)-reducing or Fe(II)-oxidizing Bacteria: A Genomic Perspective  

SciTech Connect

Originally discovered in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), the Mtr (i.e., metal-reducing) pathway exists in all characterized strains of metal-reducing Shewanella. The protein components identified to date for the Mtr pathway of MR-1 include four multi-heme c-type cytochromes (c-Cyts), CymA, MtrA, MtrC and OmcA, and a porin-like, outer membrane protein MtrB. They are strategically positioned along the width of the MR-1 cell envelope to mediate electron transfer from the quinone/quinol pool in the inner-membrane to the Fe(III)-containing minerals external to the bacterial cells. A survey of microbial genomes revealed homologues of the Mtr pathway in other dissimilatory Fe(III)-reducing bacteria, including Aeromonas hydrophila, Ferrimonas balearica and Rhodoferax ferrireducens, and in the Fe(II)-oxidizing bacteria Dechloromonas aromatica RCB, Gallionella capsiferriformans ES-2 and Sideroxydans lithotrophicus ES-1. The widespread distribution of Mtr pathways in Fe(III)-reducing or Fe(II)-oxidizing bacteria emphasizes the importance of this type of extracellular electron transfer pathway in microbial redox transformation of Fe. Their distribution in these two different functional groups of bacteria also emphasizes the bi-directional nature of electron transfer reactions carried out by the Mtr pathways. The characteristics of the Mtr pathways may be shared by other pathways used by microorganisms for exchanging electrons with their extracellular environments.

Shi, Liang; Rosso, Kevin M.; Zachara, John M.; Fredrickson, Jim K.

2012-12-01

165

Unique properties of the Mtr4p-poly(A) complex suggest a role in substrate targeting.  

PubMed

Mtr4p is a DEVH-box helicase required for 3'-end processing and degradation of various nuclear RNA substrates. In particular, Mtr4p is essential for the creation of 5.8S rRNA, U4 snRNA, and some snoRNAs and for the degradation of cryptic unstable transcripts (CUTs), aberrant mRNAs, and aberrant tRNAs. Many instances of 3'-end processing require limited polyadenylation to proceed. While polyadenylation can signal degradation in species from bacteria to humans, the mechanism whereby polyadenylated substrates are delivered to the degradation machinery is unknown. Our previous work has shown that Mtr4p preferentially binds poly(A) RNA. We suspect that this preference aids in targeting polyadenylated RNAs to the exosome. In these studies, we have investigated the mechanism underlying the preference of Mtr4p for poly(A) substrates as a means of understanding how Mtr4p might facilitate targeting. Our analysis has revealed that recognition of poly(A) substrates involves sequence-specific changes in the architecture of Mtr4p-RNA complexes. Furthermore, these differences significantly affect downstream activities. In particular, homopolymeric stretches like poly(A) ineffectively stimulate the ATPase activity of Mtr4p and suppress the rate of dissociation of the Mtr4p-RNA complex. These findings indicate that the Mtr4p-poly(A) complex is unique and ideally suited for targeting key substrates to the exosome. PMID:21058657

Bernstein, Jade; Ballin, Jeff D; Patterson, Dimeka N; Wilson, Gerald M; Toth, Eric A

2010-11-19

166

Unique properties of the Mtr4p-poly(A) complex suggest a role in substrate targeting†  

PubMed Central

Mtr4p is a DEVH-box helicase required for 3?-end processing and degradation of various nuclear RNA substrates. In particular, Mtr4p is essential for the creation of 5.8S rRNA, U4 snRNA, and some snoRNAs, and for the degradation of cryptic unstable transcripts (CUTs), aberrant mRNAs and aberrant tRNAs. Many instances of 3?-end processing require limited polyadenylation to proceed. While polyadenylation can signal degradation in species from bacteria to humans, the mechanism whereby polyadenylated substrates are delivered to the degradation machinery is unknown. Our previous work has shown that Mtr4p preferentially binds poly(A) RNA. We suspect that this preference aids in targeting polyadenylated RNAs to the exosome. In these studies, we have investigated the mechanism underlying the preference of Mtr4p for poly(A) substrates as a means to understand how Mtr4p might facilitate targeting. Our analysis has revealed that recognition of poly(A) substrates involves sequence-specific changes in the architecture of Mtr4p-RNA complexes. Furthermore, these differences significantly affect downstream activities. In particular, homopolymeric stretches like poly(A) ineffectively stimulate the ATPase activity of Mtr4p and suppress the rate of Mtr4p-RNA complex dissociation. These findings indicate that the Mtr4p-poly(A) complex is unique and ideally suited for targeting key substrates to the exosome.

Bernstein, Jade; Ballin, Jeff D.; Patterson, Dimeka N.; Wilson, Gerald M.; Toth, Eric A.

2010-01-01

167

Haploinsufficiency of mTR results in defects in telomere elongation.  

PubMed

Telomeres are usually maintained about an equilibrium length, and the set point for this equilibrium differs between species and between strains of a given species. To examine the requirement for telomerase in mediating establishment of a new telomere length equilibrium, we generated interspecies crosses with telomerase mTR knockout mice. In crosses between C57BL/6J (B6) and either of two unrelated mouse species, CAST/Ei and SPRET/Ei, telomerase mediated establishment of a new telomere length equilibrium in wild-type mTR(+/+) mice. This new equilibrium was characterized by elongation of the short telomeres of CAST/Ei or SPRET/Ei origin. In contrast, mTR(-/-) offspring of interspecies crosses failed to elongate telomeres. Unexpectedly, haploinsufficiency was observed in mTR(+/-) heterozygous interspecies mice, which had an impaired ability to elongate short SPRET/Ei or CAST/Ei telomeres to the new equilibrium set point that was achieved in wild-type mTR(+/+) mice. These results demonstrate that elongation of telomeres to a new telomere set point requires telomerase and indicate that telomerase RNA may be limiting in vivo. PMID:11904421

Hathcock, Karen S; Hemann, Michael T; Opperman, Kay Keyer; Strong, Margaret A; Greider, Carol W; Hodes, Richard J

2002-03-19

168

Haploinsufficiency of mTR results in defects in telomere elongation  

PubMed Central

Telomeres are usually maintained about an equilibrium length, and the set point for this equilibrium differs between species and between strains of a given species. To examine the requirement for telomerase in mediating establishment of a new telomere length equilibrium, we generated interspecies crosses with telomerase mTR knockout mice. In crosses between C57BL/6J (B6) and either of two unrelated mouse species, CAST/Ei and SPRET/Ei, telomerase mediated establishment of a new telomere length equilibrium in wild-type mTR+/+ mice. This new equilibrium was characterized by elongation of the short telomeres of CAST/Ei or SPRET/Ei origin. In contrast, mTR?/? offspring of interspecies crosses failed to elongate telomeres. Unexpectedly, haploinsufficiency was observed in mTR+/? heterozygous interspecies mice, which had an impaired ability to elongate short SPRET/Ei or CAST/Ei telomeres to the new equilibrium set point that was achieved in wild-type mTR+/+ mice. These results demonstrate that elongation of telomeres to a new telomere set point requires telomerase and indicate that telomerase RNA may be limiting in vivo.

Hathcock, Karen S.; Hemann, Michael T.; Opperman, Kay Keyer; Strong, Margaret A.; Greider, Carol W.; Hodes, Richard J.

2002-01-01

169

Spontaneous Mutation at the mtr Locus in Neurospora: The Molecular Spectrum in Wild-Type and a Mutator Strain  

Microsoft Academic Search

Sequence analysis of 34 mtr mutations has yielded the first molecular spectrum of spontaneous mutants in Neurospora crassa. The great majority of the mutations are base substitutions (48%) or deletions (35%). In addition, sequence analysis of the entire mtr region, including the 1472-base pair open reading frame and 1205 base pairs of flanking DNA, was performed in both the Oak

Davin Dillon; David Stadler

170

Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis  

Microsoft Academic Search

Objectives: To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant disability; and to assess whether grey or white matter MTR measures are associated with clinical measures of impairment in early RRMSMethods: 38 patients were studied (mean disease duration 1.9 years

G R Davies; L Ramio?-Torrenta?; A Hadjiprocopis; D T Chard; C M B Griffin; W Rashid; G J Barker; R Kapoor; A J Thompson; D H Miller

2004-01-01

171

Role of Mex67-Mtr2 in the Nuclear Export of 40S Pre-Ribosomes  

PubMed Central

Nuclear export of mRNAs and pre-ribosomal subunits (pre40S and pre60S) is fundamental to all eukaryotes. While genetic approaches in budding yeast have identified bona fide export factors for mRNAs and pre60S subunits, little is known regarding nuclear export of pre40S subunits. The yeast heterodimeric transport receptor Mex67-Mtr2 (TAP-p15 in humans) binds mRNAs and pre60S subunits in the nucleus and facilitates their passage through the nuclear pore complex (NPC) into the cytoplasm by interacting with Phe-Gly (FG)-rich nucleoporins that line its transport channel. By exploiting a combination of genetic, cell-biological, and biochemical approaches, we uncovered an unanticipated role of Mex67-Mtr2 in the nuclear export of 40S pre-ribosomes. We show that recruitment of Mex67-Mtr2 to pre40S subunits requires loops emanating from its NTF2-like domains and that the C-terminal FG-rich nucleoporin interacting UBA-like domain within Mex67 contributes to the transport of pre40S subunits to the cytoplasm. Remarkably, the same loops also recruit Mex67-Mtr2 to pre60S subunits and to the Nup84 complex, the respective interactions crucial for nuclear export of pre60S subunits and mRNAs. Thus Mex67-Mtr2 is a unique transport receptor that employs a common interaction surface to participate in the nuclear export of both pre-ribosomal subunits and mRNAs. Mex67-Mtr2 could engage a regulatory crosstalk among the three major export pathways for optimal cellular growth and proliferation.

Occhipinti, Laura; Kemmler, Stefan; Panse, Vikram G.

2012-01-01

172

The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing  

SciTech Connect

The essential RNA helicase, Mtr4, performs a critical role in RNA processing and degradation as an activator of the nuclear exosome. The molecular basis for this vital function is not understood and detailed analysis is significantly limited by the lack of structural data. In this study, we present the crystal structure of Mtr4. The structure reveals a new arch-like domain that is specific to Mtr4 and Ski2 (the cytosolic homologue of Mtr4). In vivo and in vitro analyses demonstrate that the Mtr4 arch domain is required for proper 5.8S rRNA processing, and suggest that the arch functions independently of canonical helicase activity. In addition, extensive conservation along the face of the putative RNA exit site highlights a potential interface with the exosome. These studies provide a molecular framework for understanding fundamental aspects of helicase function in exosome activation, and more broadly define the molecular architecture of Ski2-like helicases.

Jackson, R.N.; Robinson, H.; Klauer, A. A.; Hintze, B. J.; van Hoof, A.; Johnson, S. J.

2010-07-01

173

MTR WING, TRA604, INTERIOR. BASEMENT. INTERIOR VIEW FROM SAME LOCATION ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR WING, TRA-604, INTERIOR. BASEMENT. INTERIOR VIEW FROM SAME LOCATION IN WEST CORRIDOR AS PHOTO ID-33-G-42 BUT CAMERA FACES SOUTH. SIGN ON DOOR FOR "PIPE TUNNEL" WARNS OF RADIOLOGICAL AND ASBESTOS HAZARDS. DOOR HAS METAL HASPS. SIGN ON OVERHEAD WASTE HEAT RECOVERY PIPES SAYS THEY CONTAIN "ASBESTOS FREE INSULATION." FIRE DOOR AT LEFT LEADS TO STAIRWAY TO FIRST FLOOR. DOOR AT RIGHT LEADS TO ROOM WHICH ONCE CONTAINED MTR LIBRARY. INL NEGATIVE NO. HD46-13-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

174

Gene–nutrient and gene–gene interactions of controlled folate intake by Japanese women  

Microsoft Academic Search

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n=300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p<0.001) in young women

Mami Hiraoka; Kumiko Kato; Yoko Saito; Kazuto Yasuda; Yasuo Kagawa

2004-01-01

175

Polymorphism of cytosolic serine hydroxymethyltransferase, estrogen and breast cancer risk among Chinese women in Taiwan  

Microsoft Academic Search

Cytosolic serine hydroxymethyltransferase (cSHMT) is key to intersection of folate-metabolic pathway, participating in the pyrimidine synthesis for DNA repair. Based on the\\u000a hypothesis that variants of the cSHMT\\u000a C1420T together with methionine synthase (MS A2756G) and 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) are associated with breast cancer, we performed a multigenic case–control study of the effects to breast cancer risk

Chun-Wen Cheng; Jyh-Cherng Yu; Chiun-Sheng Huang; Jia-Ching Shieh; Yi-Ping Fu; Hsiao-Wei Wang; Pei-Ei Wu; Chen-Yang Shen

2008-01-01

176

Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk: the self defense forces study.  

PubMed

Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (?30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas. PMID:22407825

Yoshimitsu, Shinichiro; Morita, Makiko; Hamachi, Tadamichi; Tabata, Shinji; Abe, Hiroshi; Tajima, Osamu; Uezono, Kousaku; Ohnaka, Keizo; Kono, Suminori

2012-03-07

177

MTR BUILDING INTERIOR, TRA603. BASEMENT. CAMERA IS IN SOUTHWEST QUADRANT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. BASEMENT. CAMERA IS IN SOUTHWEST QUADRANT OF BASEMENT AND FACING NORTHEAST. PANEL DISPLAYS DATA READOUTS. INL NEGATIVE NO. HD46-6-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

178

Active neutron coincidence counting for the assay of MTR fuel elements  

Microsoft Academic Search

The active well coincidence counter (AWCC) and the neutron coincidence collar (CC) were investigated for their suitability to assay materials testing reactor (MTR) fuel elements. The AWCC was used with its special insert to hold the fuel element and interrogation source. The CC was modified by the addition of polyethylene liners 2.5 cm (1 in.) thick on the sides. For

Sher

1983-01-01

179

Analysis of loss of coolant accident in MTR pool type research reactor  

Microsoft Academic Search

In MTR research reactors, heat removal is, safely performed by forced convection during normal operation and by natural convection after reactor shutdown for residual decay heat removal. However, according to the duration time of operation at full power, it may be required to maintain the forced convection, for a certain period of time after the reactor shutdown. This is among

Tewfik Hamidouche; El-Khider Si-Ahmed

2011-01-01

180

MTR, TRA603. FOUNDATION PLAN, SECTION C THROUGH COOLANT WATER EXIT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. FOUNDATION PLAN, SECTION C THROUGH COOLANT WATER EXIT TUNNEL ALONG NORTH SIDE AS IT RETURNS TO MAIN COOLANT TUNNEL LEAVING BUILDING TO THE NORTH. BLAW-KNOX 3150-803-35, 5/1950. INL INDEX NO. 531-0603-62-098-100591, REV. 2. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

181

MTR, TRA603. SUBBASEMENT FLOOR PLAN. INLET/OUTLET TUNNELS FOR COOLANT WATER ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. SUB-BASEMENT FLOOR PLAN. INLET/OUTLET TUNNELS FOR COOLANT WATER (NORTH SIDE) AND AIR (SOUTH SIDE). RABBIT CANAL AND BULKHEADS. SUMPS AND DRAINS. BLAW-KNOX 3150-3-7, 3/1950. INL INDEX NO. 531-0603-00-098-100006, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

182

MTR, TRA603. SUBPILE ROOM PLAN AND SECTIONS. CONCRETE FILL AT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. SUB-PILE ROOM PLAN AND SECTIONS. CONCRETE FILL AT TWO ELEVATIONS. EXIT AIR DUCT. EXIT AND INLET WATER. PEBBLE CUBICLE AND BIN. BLAW-KNOX 3150-803-45, 9/1950. INL INDEX NO. 531-0603-62-098-100601, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

183

MTR, TRA603. FOUNDATION PLAN, SECTION A ALONG NORTH/SOUTH AXIS SHOWS ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. FOUNDATION PLAN, SECTION A ALONG NORTH/SOUTH AXIS SHOWS PIPE TUNNEL FOR COOLANT WATER. BLAW-KNOX 3150-803-33, 5/1950. INL INDEX NO. 531-0603-62-098-100589, REV. 8. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

184

MTR STACK, TRA710, DETAIL OF BASE. CAMERA FACING NORTH. SIGN ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR STACK, TRA-710, DETAIL OF BASE. CAMERA FACING NORTH. SIGN SAYS "DANGER, DO NOT USE THIS LADDER." TRA-605, PROCESS WATER BUILDING, IN VIEW AT LEFT. INL NEGATIVE NO. HD52-1-3. Mike Crane, Photographer, 5/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

185

MTR COMPRESSOR BUILDING, TRA651. TWO JOY COMPRESSORS ARE INSTALLED. OUT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR COMPRESSOR BUILDING, TRA-651. TWO JOY COMPRESSORS ARE INSTALLED. OUT OF VIEW ON RIGHT WERE TWO INGERSOLL-RAND COMPRESSORS. NOTE FRAME STRUCTURE OF METAL-SIDING BUILDING. COMPARE WITH ID-33-G-4. INL NEGATIVE NO. 56-1257. Jack L. Anderson, Photographer, 4/20/1956 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

186

MTR BUILDING, TRA603. NORTHEAST CORNER, NORTH SIDE SHADED. CAMERA FACING ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING, TRA-603. NORTHEAST CORNER, NORTH SIDE SHADED. CAMERA FACING SOUTHWEST. NORTH-SIDE PROJECTION IS PLUG STORAGE BUILDING, TRA-657; BUILDING NEXT TO EAST WALL IS AIR COMPRESSOR BUILDING, TRA-626. INL NEGATIVE NO. HD46-43-1. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

187

MTR, TRA603. CANAL, PLANS AND TRANSVERSE SECTION. FOUNDATION PLAN. COUNTERFORT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. CANAL, PLANS AND TRANSVERSE SECTION. FOUNDATION PLAN. COUNTERFORT SUPPORTS. DRAINS. SUMPS. CRANE RAIL. HATCHWAYS. BLAW-KNOX 3150-803-2, 4/1950. INL INDEX NO. 531-0603-62-098-100582, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

188

MTR, TRA603. FOUNDATION PLAN, SECTION B ALONG EAST/WEST AXIS SHOWS ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. FOUNDATION PLAN, SECTION B ALONG EAST/WEST AXIS SHOWS TUNNELS, SUB-PILE ROOM SHIELDING AND OPENINGS, CANAL AND RELATED SECTIONS. BLAW-KNOX 3150-803-34, 5/1950. INL INDEX NO. 531-0603-62-098-100590, REV. 7. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

189

MTR WING, TRA604. BASEMENT FLOOR PLAN. FIREPROOF RECORD ROOM BELOW ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR WING, TRA-604. BASEMENT FLOOR PLAN. FIRE-PROOF RECORD ROOM BELOW COUNTING ROOM. HEATING AND COOLING EQUIPMENT. UNSPECIFIED EXPANSION AREA ALONG WEST WALL. BLAW-KNOX 3150-4-1, 7/1950. INL INDEX NO. 531-0604-00-098-100007, REV. 1. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

190

MTR, TRA603. FOUNDATION PLAN FOR AREA JUST BELOW BASEMENT FLOOR. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. FOUNDATION PLAN FOR AREA JUST BELOW BASEMENT FLOOR. CAISSON COLUMN REINFORCEMENT. AIR DUCTS. BLAW-KNOX 3150-803-31, 5/1950. INL INDEX NO. 531-0603-62-098-100587, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

191

EVALUATION OF FISSION GAS ADSORPTION TRAPS FOR ORNL-MTR-44 LOOP EXPERIMENT  

Microsoft Academic Search

A method of predicting the performance of fission gas adsorption traps ; containing activated charcoal is presented. This method is applied in the ; evaluation of the fission gas traps designed for use in the ORNL-MTR44 loop ; experiment. The method should also be applicable in evaluating fission gas traps ; contained in other reactor experiments. (auth);

R. E. Adams; W. E. Browning

1958-01-01

192

MTR STACK, TRA71, DETAIL OF PUMICE BLOCK SERVICE BUILDING AT ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR STACK, TRA-71-, DETAIL OF PUMICE BLOCK SERVICE BUILDING AT BASE OF STACK. CAMERA FACING SOUTHEAST. INL NEGATIVE NO. HD52-1-2. Mike Crane, Photographer, 5/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

193

MTR BUILDING INTERIOR, TRA603. CAMERA FACING SOUTHEAST CORNER OF REACTOR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA FACING SOUTHEAST CORNER OF REACTOR FLOOR. SUPPLIES AND EQUIPMENT RELATE TO MOCK-UP PROJECT. NOTE PRECAST WALL PANELS SUPPORTED BY VERTICAL COLUMNS OF REINFORCED CONCRETE. INL NEGATIVE NO. HD46-4-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

194

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON REACTOR FLOOR, FACING NORTHEAST, THE WEST AND SOUTH FACES OF THE REACTOR. MOCK-UP APPARATUS IS AT RIGHT OF VIEW. INL NEGATIVE NO. HD-46-3-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

195

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON WEST FACE OF REACTOR. SHIELDING BLOCKS IN FOREGROUND ATOP CABINET. INL NEGATIVE NO. HD46-3-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

196

REACTOR SERVICES BUILDING, TRA635. EAST SIDE. CAMERA LOOKING NORTHWEST. MTR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

REACTOR SERVICES BUILDING, TRA-635. EAST SIDE. CAMERA LOOKING NORTHWEST. MTR BUILDING, TRA-603, AT RIGHT OF VIEW. INL NEGATIVE NO. HD46-41-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

197

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED BY EAST WALL ON LEFT AND APPARATUS ON RIGHT. CAMERA FACING SOUTH. INL NEGATIVE NO. HD46-1-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

198

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. DETAIL OF REACTOR'S SOUTH ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. DETAIL OF REACTOR'S SOUTH FACE. CAMERA FACING NORTHWESTERLY. INL NEGATIVE NO. HD46-1-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

199

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. DETAIL OF REACTOR TEST ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. DETAIL OF REACTOR TEST HOLE OPENING IN WEST FACE. CAMERA FACING NORTHEAST. INL NEGATIVE NO. HD46-2-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

200

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF THIRD FLOOR BALCONY LOOKING SOUTHEAST. DETAIL OF REACTOR'S NORTH FACE AND ITS TEST HOLES. MOCK-UP APPARATUS IS BEYOND REACTOR. INL NEGATIVE NO. HD46-5-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

201

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT SOUTH END OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT SOUTH END OF THIRD FLOOR BALCONY LOOKING NORTHEAST. BRIDGE BETWEEN BALCONY AND REACTOR TOP AT LEFT OF VIEW. INL NEGATIVE NO. HD46-5-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

202

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. CONTEXTUAL VIEW OF SOUTHWEST ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. CONTEXTUAL VIEW OF SOUTHWEST CORNER OF REACTOR. WEST FACE IS TOWARD LEFT OF VIEW. CAMERA FACING NORTHEAST. INL NEGATIVE NO. HD46-2-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

203

REACTOR SERVICES BUILDING, TRA635. WEST SIDE. CAMERA LOOKING NORTHEAST. MTR ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

REACTOR SERVICES BUILDING, TRA-635. WEST SIDE. CAMERA LOOKING NORTHEAST. MTR (TRA-603) AT LEFT OF VIEW. INL NEGATIVE NO. HD46-41-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

204

Mind the gap: diversity and reactivity relationships among multihaem cytochromes of the MtrA/DmsE family.  

PubMed

Shewanella oneidensis MR-1 has the ability to use many external terminal electron acceptors during anaerobic respiration, such as DMSO. The pathway that facilitates this electron transfer includes the decahaem cytochrome DmsE, a paralogue of the MtrA family of decahaem cytochromes. Although both DmsE and MtrA are decahaem cytochromes implicated in the long-range electron transfer across a ~300 Å (1 Å=0.1 nm) wide periplasmic 'gap', MtrA has been shown to be only 105 Å in maximal length. In the present paper, DmsE is further characterized via protein film voltammetry, revealing that the electrochemistry of the DmsE haem cofactors display macroscopic potentials lower than those of MtrA by 100 mV. It is possible this tuning of the redox potential of DmsE is required to shuttle electrons to the outer-membrane proteins specific to DMSO reduction. Other decahaem cytochromes found in S. oneidensis, such as the outer-membrane proteins MtrC, MtrF and OmcA, have been shown to have electrochemical properties similar to those of MtrA, yet possess a different evolutionary relationship. PMID:23176466

Bewley, Kathryn D; Firer-Sherwood, Mackenzie A; Mock, Jee-Young; Ando, Nozomi; Drennan, Catherine L; Elliott, Sean J

2012-12-01

205

Towards Electrosynthesis in Shewanella: Energetics of Reversing the Mtr Pathway for Reductive Metabolism  

PubMed Central

Bioelectrochemical systems rely on microorganisms to link complex oxidation/reduction reactions to electrodes. For example, in Shewanella oneidensis strain MR-1, an electron transfer conduit consisting of cytochromes and structural proteins, known as the Mtr respiratory pathway, catalyzes electron flow from cytoplasmic oxidative reactions to electrodes. Reversing this electron flow to drive microbial reductive metabolism offers a possible route for electrosynthesis of high value fuels and chemicals. We examined electron flow from electrodes into Shewanella to determine the feasibility of this process, the molecular components of reductive electron flow, and what driving forces were required. Addition of fumarate to a film of S. oneidensis adhering to a graphite electrode poised at ?0.36 V versus standard hydrogen electrode (SHE) immediately led to electron uptake, while a mutant lacking the periplasmic fumarate reductase FccA was unable to utilize electrodes for fumarate reduction. Deletion of the gene encoding the outer membrane cytochrome-anchoring protein MtrB eliminated 88% of fumarate reduction. A mutant lacking the periplasmic cytochrome MtrA demonstrated more severe defects. Surprisingly, disruption of menC, which prevents menaquinone biosynthesis, eliminated 85% of electron flux. Deletion of the gene encoding the quinone-linked cytochrome CymA had a similar negative effect, which showed that electrons primarily flowed from outer membrane cytochromes into the quinone pool, and back to periplasmic FccA. Soluble redox mediators only partially restored electron transfer in mutants, suggesting that soluble shuttles could not replace periplasmic protein-protein interactions. This work demonstrates that the Mtr pathway can power reductive reactions, shows this conduit is functionally reversible, and provides new evidence for distinct CymA:MtrA and CymA:FccA respiratory units.

Ross, Daniel E.; Flynn, Jeffrey M.; Baron, Daniel B.; Gralnick, Jeffrey A.; Bond, Daniel R.

2011-01-01

206

Shewanella putrefaciens mtrB Encodes an Outer Membrane Protein Required for Fe(III) and Mn(IV) Reduction  

PubMed Central

Iron and manganese oxides or oxyhydroxides are abundant transition metals, and in aquatic environments they serve as terminal electron acceptors for a large number of bacterial species. The molecular mechanisms of anaerobic metal reduction, however, are not understood. Shewanella putrefaciens is a facultative anaerobe that uses Fe(III) and Mn(IV) as terminal electron acceptors during anaerobic respiration. Transposon mutagenesis was used to generate mutants of S. putrefaciens, and one such mutant, SR-21, was analyzed in detail. Growth and enzyme assays indicated that the mutation in SR-21 resulted in loss of Fe(III) and Mn(IV) reduction but did not affect its ability to reduce other electron acceptors used by the wild type. This deficiency was due to Tn5 inactivation of an open reading frame (ORF) designated mtrB. mtrB encodes a protein of 679 amino acids and contains a signal sequence characteristic of secreted proteins. Analysis of membrane fractions of the mutant, SR-21, and wild-type cells indicated that MtrB is located on the outer membrane of S. putrefaciens. A 5.2-kb DNA fragment that contains mtrB was isolated and completely sequenced. A second ORF, designated mtrA, was found directly upstream of mtrB. The two ORFs appear to be arranged in an operon. mtrA encodes a putative 10-heme c-type cytochrome of 333 amino acids. The N-terminal sequence of MtrA contains a potential signal sequence for secretion across the cell membrane. The amino acid sequence of MtrA exhibited 34% identity to NrfB from Escherichia coli, which is involved in formate-dependent nitrite reduction. To our knowledge, this is the first report of genes encoding proteins involved in metal reduction.

Beliaev, Alexander S.; Saffarini, Daad A.

1998-01-01

207

Human cytomegalovirus mtrII oncoprotein binds to p53 and down-regulates p53-activated transcription.  

PubMed Central

The 79-amino-acid (79-aa) open reading frame (UL111a) gene within morphological transforming region II (mtrII) of human cytomegalovirus strain Towne has been shown to transform rodent cells in vitro (J. Thompson, J. Doniger, and L. J. Rosenthal, Arch. Virol. 136:161-172, 1994). Moreover, a translation termination linker (TTL) mutant of mtrII that coded for the first 49 aa of mtrII oncoprotein (designated TTL49) was sufficient for malignant transformation, whereas a TTL mutant that coded for the first 24 aa (designated TTL24) was not. The current study demonstrates the binding of mtrII oncoprotein to the tumor suppressor protein p53 both in vivo using transiently transfected cells and in vitro using labeled proteins. Furthermore, the C-terminally truncated mtrII protein TTL49, but not truncated protein TTL24, bound to p53. The mtrII binding domain mapped to the N-terminal region of p53, residues 1 to 106, with a critical region from aa 27 to 44, whereas the p53 binding domain of mtrII protein was the first 49 aa. Furthermore, mtrII inhibited p53-activated transcription, indicating its ability to alter p53-directed cellular regulatory mechanisms. mtrII oncoprotein was detected both in stably transfected NIH 3T3 cell lines and human cytomegalovirus-infected HEL 299 cells (as early as 12 h after infection) in the perinuclear region and in the nucleus. mtrII-transformed cell lines, at both early and late passage, exhibited high levels of p53 with a 15-fold-extended half-life. However, p53-activated transcription was suppressed in these cells in spite of the increased p53 levels. Finally, the results with wild-type mtrII and its TTL mutants with respect to p53 binding, p53-activated transcription, and transforming ability suggest that the mechanism of mtrII transformation is linked to both p53 binding and disruption of p53 cell regulation.

Muralidhar, S; Doniger, J; Mendelson, E; Araujo, J C; Kashanchi, F; Azumi, N; Brady, J N; Rosenthal, L J

1996-01-01

208

Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.  

PubMed

Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a case-control study nested within the UK population-based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight polymorphisms: MTHFR C677T (rs1801133; 12 studies; 10,745 cases; 40,158 controls), MTHFR A1298C (rs1801131; 5 studies; 3,176 cases; 4,829 controls), MTR A2756G (rs1805087; 8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 controls), and FOLH1 T1561C (rs202676; 5 studies; 6,314 cases; 35,190 controls). The majority (10 of 13) of eligible studies had 100% Caucasian subjects; only one study had <90% Caucasian subjects. We found weak evidence of dominant effects of two alleles: MTR 2756A>G [random effects pooled odds ratio, 1.06 (1.00-1.12); P = 0.06 (P = 0.59 for heterogeneity across studies)] and SHMT1 1420C>T [random effects pooled odds ratio, 1.11 (1.00-1.22); P = 0.05 (P = 0.38 for heterogeneity across studies)]. We found no effect of MTHFR 677C>T or any of the other alleles in dominant, recessive or additive models, or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on advanced or localized cancers. Our meta-analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer. PMID:19706844

Collin, Simon M; Metcalfe, Chris; Zuccolo, Luisa; Lewis, Sarah J; Chen, Lina; Cox, Angela; Davis, Michael; Lane, J Athene; Donovan, Jenny; Smith, George Davey; Neal, David E; Hamdy, Freddie C; Gudmundsson, Julius; Sulem, Patrick; Rafnar, Thorunn; Benediktsdottir, Kristrun R; Eeles, Rosalind A; Guy, Michelle; Kote-Jarai, Zsofia; Morrison, Jonathan; Al Olama, Ali Amin; Stefansson, Kari; Easton, Douglas F; Martin, Richard M

2009-08-25

209

Extracellular Reduction of Hexavalent Chromium by Cytochromes MtrC and OmcA of Shewanella oneidensis MR-1 ?  

PubMed Central

To characterize the roles of cytochromes MtrC and OmcA of Shewanella oneidensis MR-1 in Cr(VI) reduction, the effects of deleting the mtrC and/or omcA gene on Cr(VI) reduction and the cellular locations of reduced Cr(III) precipitates were investigated. Compared to the rate of reduction of Cr(VI) by the wild type (wt), the deletion of mtrC decreased the initial rate of Cr(VI) reduction by 43.5%, while the deletion of omcA or both mtrC and omcA lowered the rate by 53.4% and 68.9%, respectively. In wt cells, Cr(III) precipitates were detected by transmission electron microscopy in the extracellular matrix between the cells, in association with the outer membrane, and inside the cytoplasm. No extracellular matrix-associated Cr(III) precipitates, however, were found in the cytochrome mutant cell suspension. In mutant cells without either MtrC or OmcA, most Cr(III) precipitates were found in association with the outer membrane, while in mutant cells lacking both MtrC and OmcA, most Cr(III) precipitates were found inside the cytoplasm. Cr(III) precipitates were also detected by scanning election microscopy on the surfaces of the wt and mutants without MtrC or OmcA but not on the mutant cells lacking both MtrC and OmcA, demonstrating that the deletion of mtrC and omcA diminishes the extracellular formation of Cr(III) precipitates. Furthermore, purified MtrC and OmcA reduced Cr(VI) with apparent kcat values of 1.2 ± 0.2 (mean ± standard deviation) and 10.2 ± 1 s?1 and Km values of 34.1 ± 4.5 and 41.3 ± 7.9 ?M, respectively. Together, these results consistently demonstrate that MtrC and OmcA are the terminal reductases used by S. oneidensis MR-1 for extracellular Cr(VI) reduction where OmcA is a predominant Cr(VI) reductase.

Belchik, Sara M.; Kennedy, David W.; Dohnalkova, Alice C.; Wang, Yuanmin; Sevinc, Papatya C.; Wu, Hong; Lin, Yuehe; Lu, H. Peter; Fredrickson, James K.; Shi, Liang

2011-01-01

210

Increased prevalence of combined MTR and MTHFR genotypes among individuals with severely elevated total homocysteine plasma levels  

Microsoft Academic Search

The prevalence of the methionine synthase (MTR) 2756A?G polymorphism among individuals with severely elevated total homocysteine (tHcy) plasma levels is unknown. Therefore, 1,716 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, 733 kidney graft recipients, and 389 healthy subjects, were investigated. The distribution of MTR 2756A?G, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C?T\\/1298A?C, genotypes among study participants with extremely

Alexandra Feix; Robert Fritsche-Polanz; Josef Kletzmayr; Andreas Vychytil; Walter H. Hörl; Gere Sunder-Plassmann; Manuela Födinger

2001-01-01

211

MTR BUILDING, TRA603. EAST SIDE. CAMERA FACING WEST. CORRUGATED IRON ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING, TRA-603. EAST SIDE. CAMERA FACING WEST. CORRUGATED IRON BUILDING MARKED WITH "X" IS TRA-651. TRA-626, TO ITS RIGHT, HOUSED COMPRESSOR EQUIPMENT FOR THE AIRCRAFT NUCLEAR PROPULSION PROGRAM. LATER, IT WAS USED FOR STORAGE. INL NEGATIVE NO. HD46-42-4. Mike Crane, Photographer, April 2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

212

CFD simulation of the IAEA 10 MW generic MTR reactor under loss of flow transient  

Microsoft Academic Search

Three-dimensional simulation of the IAEA 10MW generic reactor under loss of flow transient is introduced using the CFD code, Fluent. The IAEA reactor calculation is a safety-related benchmark problem for an idealized material testing reactor (MTR) pool type specified in order to compare calculational methods used in various research centers. The flow transients considered include fast loss of flow accidents

Amgad Salama; Salah El-Din El-Morshedy

2011-01-01

213

MTR WING, TRA604. PRECAST CONCRETE PANELS AND DIMENSIONS. TYPES A, ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR WING, TRA-604. PRECAST CONCRETE PANELS AND DIMENSIONS. TYPES A, B, C, D, E, AND F; AND HOW THEY ARE CONNECTED. TYPES C AND D ARE ON WEST SIDE WHERE GLASS BLOCKS SURROUND ENTRY DOOR. BLAW-KNOX 3150-804-20, SHEET #1, 11/1950. INL INDEX NO. 531-0604-62-098-100644, REV. 0. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

214

MTR, TRA603. TRANSVERSE SECTION LOOKS DOWN EAST/WEST AXIS TO SHOW ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. TRANSVERSE SECTION LOOKS DOWN EAST/WEST AXIS TO SHOW PATH OF PROCESS WATER LINES IN PIPE TUNNEL FROM SUMP PUMP, AIR DUCTS, ELEVATORS, CANAL IN BASEMENT LEVEL, CANAL CRANE DOWN CENTER LINE OF CANAL, AND REACTOR ROOM CRANE ON TRAVELING RAIL. BLAW-KNOX BKC-3150, 3/1950. INL INDEX NO. 531-0603-00-098-100005, REV. 4. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

215

Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS  

Microsoft Academic Search

ObjectiveTo investigate whether T2 lesion load and magnetisation transfer ratio (MTR) in the normal-appearing white matter (NAWM) and grey matter (GM) at study entry are independent predictors of progression and whether their changes correlate with the accrual of disability, over 5 years in early primary progressive multiple sclerosis (PPMS).MethodsForty-seven patients with early PPMS and 18 healthy controls were recruited at

C Tur; Z Khaleeli; O Ciccarelli; D R Altmann; M Cercignani; D H Miller; A J Thompson

2010-01-01

216

MTR, TRA603. SECOND FLOOR PLAN. OFFICES AND INSTRUMENT ROOM. STEEL ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. SECOND FLOOR PLAN. OFFICES AND INSTRUMENT ROOM. STEEL PARTITIONS ON EAST SIDE OF INSTRUMENT ROOM. DETAIL OF COLUMN ENCASEMENTS. STAIRWAYS IN NORTH AND SOUTH CORNERS. PASSENGER ELEVATION. BLAW-KNOX 3150-803-3, 7/1950. INL INDEX NO. 531-0603-00-098-100562, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

217

MTR, TRA603. FOUNDATION PLAN. USE AND LOCATION OF CAISSONS, WHICH ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR, TRA-603. FOUNDATION PLAN. USE AND LOCATION OF CAISSONS, WHICH SUPPORTED BASEMENT AND UPPER LEVEL OF BUILDING; CAISSON DIAMETERS. SECTIONS ARE MARKED AS REFERENTS FOR THE NEXT THREE DRAWINGS. BLAW-KNOX 3150-803-30, 5/1950. INL INDEX NO. 531-0603-62-100586, REV. 5. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

218

MTR BUILDING INTERIOR, TRA603. CAMERA IS ON SECOND FLOOR BALCONY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS ON SECOND FLOOR BALCONY LOOKING DOWN ON REACTOR FLOOR, FACING EAST. REACTOR IS AT LEFT OF VIEW. APPARATUS DIRECTLY IN FRONT OF CAMERA IS PART OF A MOCK-UP PROJECT. INL NEGATIVE NO. HD46-3-3. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

219

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF SECOND FLOOR BALCONY LOOKING TOWARDS WORK PLATFORMS ON NORTH FACE OF REACTOR. BRIDGE TO THIRD FLOOR BALCONY FROM TOP OF REACTOR IS AT UPPER RIGHT OF VIEW. CAMERA FACING EASTERLY. INL NEGATIVE NO. HD-46-4-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

220

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. CAMERA IS IN NORTHEAST ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. CAMERA IS IN NORTHEAST CORNER FACING SOUTHWEST. NORTH FACE OF REACTOR IS IN LEFT HALF OF VIEW. WEST WALL CONTAINS CONTROL BALCONIES. BRIDGE FROM REACTOR TO SECOND-FLOOR BALCONY IS IN CENTER OF VIEW. INL NEGATIVE NO. HD46-1-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

221

MTR BUILDING INTERIOR, TRA603, SECOND FLOOR BALCONY. CAMERA FACING NORTH. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, SECOND FLOOR BALCONY. CAMERA FACING NORTH. ROOMS 204, 203, 202, AND 201 ARE TO LEFT. VIEW TOWARDS REACTOR FLOOR IS SEEN THROUGH BALCONY RAILING. PLATFORM BETWEEN REACTOR AND THIRD FLOOR BALCONY IS SEEN BEYOND SQUARE PILLAR IN FOREGROUND. INL NEGATIVE NO. HD46-3-1. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

222

MTR BUILDING INTERIOR, TRA603. CAMERA IS AT NORTH END OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603. CAMERA IS AT NORTH END OF THIRD FLOOR BALCONY LOOKING SOUTHEAST AND ACROSS TOP OF REACTOR. MOCK-UP APPARATUS IS BEYOND REACTOR. BRIDGE CONNECTING BALCONY AND REACTOR TOP AT RIGHT OF VIEW. INL NEGATIVE NO. HD46-5-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

223

MTR BUILDING INTERIOR, TRA603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR BUILDING INTERIOR, TRA-603, REACTOR FLOOR. VIEW DOWN CORRIDOR CREATED BY REACTOR (LEFT OF VIEW) AND WEST WALL ON RIGHT. BRIDGE OVERHEAD PROVIDED ACCESS TO TOP OF REACTOR FROM BALCONY. NOTE WIDTH OF BRIDGE. CAMERA FACING SOUTH TOWARDS OPEN DOOR OF REACTOR SERVICE BUILDING, TRA-635. INL NEGATIVE NO. HD46-1-2. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

224

Active neutron coincidence counting for the assay of MTR fuel elements  

SciTech Connect

The active well coincidence counter (AWCC) and the neutron coincidence collar (CC) were investigated for their suitability to assay materials testing reactor (MTR) fuel elements. The AWCC was used with its special insert to hold the fuel element and interrogation source. The CC was modified by the addition of polyethylene liners 2.5 cm (1 in.) thick on the sides. For a typical MTR element (approx. 220 g /sup 235/U) and 1000-s count times, statistical errors were approx. 1.6% for the CC and approx. 0.6% for AWCC. For either instrument, the change in count rate corresponding to the removal or addition of one fuel plate (with an 18-plate element) was approx. 3.8%; thus, either instrument can detect removal of one plate. The AWCC can also detect removal of one plate in count times that are considerably less than 1000 s. Various functions were investigated to fit the coincidence count rate vs /sup 235/U mass curve for the AWCC. Programs have been written for the Hewlett-Packard HP-97 calculator to calculate the calibration constants of these functions by a least-squares technique. Coincidence count rates in the AWCC depend on the orientation of the plates of the fuel elements because of the counting efficiency variation in the insert. To lessen this dependence, the MTR element should be counted with its plates positioned vertically, that is, parallel to the radius of the device. For the collar, the effect of plate orientation is much smaller.

Sher, R.

1983-02-01

225

Localization and DNA sequence analysis of the transforming domain (mtrII) of human cytomegalovirus.  

PubMed Central

To define the morphological transforming region II (mtrII) of human cytomegalovirus (HCMV), a series of subclones of the Xba I/BamHI fragment EM was constructed in vitro and tested for focus-forming activity and tumorigenicity. A 980-base-pair subclone of fragment EM was identified, and its nucleotide sequence revealed three small open reading frames (ORFs), encoding 79, 83, and 34 amino acid residues. S1 nuclease analysis of HCMV-infected cells identified several distinct early RNA species within mtrII, two of which (P1 and P2) were of particular interest, since the length of the protected DNA fragments would position the 5' end of the RNAs upstream of the open reading frames. In addition, the 980-base-pair transforming sequence revealed DNA elements capable of forming stem-loop structures. Thus the transforming mtrII domain of HCMV strain Towne contains both small open reading frames that are expressed in lytically infected cells and sequences resembling insertion-like structures that may be involved in transformation. Images

Razzaque, A; Jahan, N; McWeeney, D; Jariwalla, R J; Jones, C; Brady, J; Rosenthal, L J

1988-01-01

226

Thermodynamics of Electron Flow in the Bacterial Deca-heme Cytochrome MtrF  

SciTech Connect

Electron transporting multiheme cytochromes are essential to the metabolism of microbes that inhabit soils and carry out important biogeochemical processes. Recently the first crystal structure of a prototype bacterial deca-heme cytochrome (MtrF) has been resolved and its electrochemistry characterized. However, the molecular details of electron conductance along heme chains in the cytochrome are difficult to access via experiment due to the nearly identical chemical nature of the heme cofactors. Here we employ large-scale molecular dynamics simulations to compute the reduction potentials of the ten hemes of MtrF in aqueous solution. We find that as a whole they fall within a range of about 0.3 V in agreement with experiment. Individual reduction potentials give rise to a free energy profile for electron conduction that is approximately symmetric with respect to the center of the protein. Our calculations indicate that there is no significant potential bias along the orthogonal octa- and tetra-heme chains suggesting that under aqueous conditions MtrF is a nearly reversible two-dimensional conductor.

Breuer, Marian; Zarzycki, Piotr P.; Blumberger, Jochen; Rosso, Kevin M.

2012-07-01

227

Radionuclide Compositions and Total Activity of Spent MTR-HEU Fuel Elements of the IAN-R1 Research Reactor  

NASA Astrophysics Data System (ADS)

With cooperation of the International Atomic Energy Agency (IAEA) and the Department of Energy (DOE) of the United States, several calculations and tasks related to the waste disposal of spent MTR fuel enriched nominally to 93% were carried out for the conversion of the IAN-R1 Research Reactor from MTR-HEU fuel to TRIGA-LEU fuel. In order to remove the spent MTR-HEU fuel of the core and store it safely a program was established at the Instituto de Ciencias Nucleares y Energìas Alternativas (INEA). This program included training, acquisition of hardware and software, design and construction of a decay pool, transfer of the spent HEU fuel elements into the decay pool and his final transport to Savannah River in United States. In this paper are presented data of activities calculated for each relevant radionuclide present in spent MTR-HEU fuel elements of the IAN-R1 Research Reactor and the total activity. The total activity calculated takes in consideration contributions of fission, activation and actinides products. The data obtained were the base for shielding calculations for the decay pool concerning the storage of spent MTR-HEU fuel elements and the respective dosimetric evaluations in the transferring operations of fuel elements into the decay pool.

Sarta, Josè A.; Castiblanco, Luis A.

2005-05-01

228

Dose Rate Calculations of Spent MTR-HEU Fuel Elements of the IAN-R1 Research Reactor  

NASA Astrophysics Data System (ADS)

With cooperation of the International Atomic Energy Agency (IAEA) and the Department of Energy (DOE) of the United States, several tasks related to the waste disposal of spent MTR fuel enriched nominally to 93% were carried out for the conversion of the IAN-R1 Research Reactor from MTR-HEU fuel to TRIGA-LEU fuel. In order to remove the spent MTR-HEU fuel of the core and store it safetly, a program was established at the Instituto de Ciencias Nucleares y Energìas Alternativas (INEA). This program included training, acquisition of hardware and sofware, design and construction of a decay pool, transfer of the spent HEU fuel elements into the decay pool and his final transport to Savanah River in United States. In this paper are presented external dose rates which were calculated for a standard spent MTR-HEU fuel element of the IAN-R1 Research Reactor. The calculations take in consideration the activity due to contributions of fission, activation and actinides products for each relevant radionuclide present in a standard spent MTR-HEU fuel. The datas obtained were the base for the respective dosimetric evaluations in the transfering operations of fuel elements into the decay pool and for shielding calculations in designing of the decay pool.

Sarta Fuentes, Jose Antonio

2005-04-01

229

Targeted Protein Degradation of Outer Membrane Decaheme Cytochrome MtrC Metal Reductase in Shewanella oneidensis MR-1 Measured Using Biarsenical Probe CrAsH-EDT2  

SciTech Connect

Development of efficient microbial biofuel cells requires an ability to exploit interfacial electron transfer reactions to external electron acceptors, such as metal oxides; such reactions occur in the facultative anaerobic gram-negative bacterium Shewanella oneidensis MR-1 through the catalytic activity of the outer membrane decaheme c-type cytochrome MtrC. Central to the utility of this pathway to synthetic biology is an understanding of cellular mechanisms that maintain optimal MtrC function, cellular localization, and renewal by degradation and resynthesis. In order to monitor trafficking to the outer membrane, and the environmental sensitivity of MtrC, we have engineered a tetracysteine tag (i.e., CCPGCC) at its C-terminus that permits labeling by the cell impermeable biarsenical fluorophore, carboxy-FlAsH (CrAsH) of MtrC at the surface of living Shewanella oneidensis MR-1 cells. In comparison, the cell permeable reagent FlAsH permits labeling of the entire population of MtrC, including proteolytic fragments resulting from incorrect maturation. We demonstrate specific labeling by CrAsH of engineered MtrC which is dependent on the presence of a functional type-2 secretion system (T2S), as evidenced by T2S system gspD or gspG deletion mutants which are incapable of CrAsH labeling. Under these latter conditions, MtrC undergoes proteolytic degradation to form a large 35-38 kDa fragment; this degradation product is also resolved during normal turnover of the CrAsH-labeled MtrC protein. No MtrC protein is released into the medium during turnover, suggesting the presence of cellular turnover systems involving MtrC reuptake and degradation. The mature MtrC localized on the outer membrane is a long-lived protein, with a turnover rate of 0.043 hr-1 that is insensitive to O2 concentration. Maturation of MtrC is relatively inefficient, with substantial rates of turnover of the immature protein prior to export to the outer membrane (i.e., 0.028 hr-1) that are consistent with the inherent complexity associated with correct heme insertion and acylation of MtrC that occurs in the periplasm prior to its targeting to the outer membrane. These latter results suggest that MtrC protein trafficking to the outer membrane and its subsequent degradation are tightly regulated, which is consistent with cellular processing pathways that target MtrC to extracellular structures and their possible role in promoting electron transfer from Shewanella to extracellular acceptors.

Xiong, Yijia; Chen, Baowei; Shi, Liang; Fredrickson, Jim K.; Bigelow, Diana J.; Squier, Thomas C.

2011-10-14

230

The use of experimental data in an MTR-type nuclear reactor safety analysis  

NASA Astrophysics Data System (ADS)

Reactivity initiated accidents (RIAs) are a category of events required for research reactor safety analysis. A subset of this is unprotected RIAs in which mechanical systems or human intervention are not credited in the response of the system. Light-water cooled and moderated MTR-type ( i.e., aluminum-clad uranium plate fuel) reactors are self-limiting up to some reactivity insertion limit beyond which fuel damage occurs. This characteristic was studied in the Borax and Spert reactor tests of the 1950s and 1960s in the USA. This thesis considers the use of this experimental data in generic MTR-type reactor safety analysis. The approach presented herein is based on fundamental phenomenological understanding and uses correlations in the reactor test data with suitable account taken for differences in important system parameters. Specifically, a semi-empirical approach is used to quantify the relationship between the power, energy and temperature rise response of the system as well as parametric dependencies on void coefficient and the degree of subcooling. Secondary effects including the dependence on coolant flow are also examined. A rigorous curve fitting approach and error assessment is used to quantify the trends in the experimental data. In addition to the initial power burst stage of an unprotected transient, the longer term stability of the system is considered with a stylized treatment of characteristic power/temperature oscillations (chugging). A bridge from the HEU-based experimental data to the LEU fuel cycle is assessed and outlined based on existing simulation results presented in the literature. A cell-model based parametric study is included. The results are used to construct a practical safety analysis methodology for determining reactivity insertion safety limits for a light-water moderated and cooled MTR-type core.

Day, Simon E.

231

DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity  

PubMed Central

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multi-directional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Kubicki, M.; Park, H.; Westin, C.F.; Nestor, P.G.; Mulkern, R.V.; Maier, S.E.; Niznikiewicz, M.; Connor, E.E.; Levitt, J.J.; Frumin, M.; Kikinis, R.; Jolesz, F.A.; McCarley, R.W.; Shenton, M.E.

2009-01-01

232

WATER PROCESS SYSTEM FLOW DIAGRAM FOR MTR, TRA603. SUMMARY OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WATER PROCESS SYSTEM FLOW DIAGRAM FOR MTR, TRA-603. SUMMARY OF COOLANT FLOW FROM WORKING RESERVOIR TO INTERIOR OF REACTOR'S THERMAL SHIELD. NAMES TANK SECTIONS. PIPE AND DRAIN-LINE SIZES. SHOWS DIRECTION OF AIR FLOW THROUGH PEBBLE AND GRAPHITE BLOCK ZONE. NEUTRON CURTAIN AND THERMAL COLUMN DOOR. BLAW-KNOX 3150-92-7, 3/1950. INL INDEX NO. 531-0603-51-098-100036, REV. 6. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

233

AFM and Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) Studies on Formation of Air-Stable Supported Lipid Bilayers  

PubMed Central

Supported lipid bilayers (SLBs) were prepared by deposition of unilamellar vesicles on a silicon substrate. Atomic force microscopy (AFM) and a new Multiple Transmission-Reflection Infrared Spectroscopy (MTR-IR) developed by us were used to trace the dynamic formation of lipid bilayers on the silicon surfaces. The evolution from deformation of vesicles to formation of bilayers can be distinguished clearly by AFM imaging. MTR-IR provided high quality infrared spectra of ultrathin lipid bilayers with high sensitivity and high signal to noise ratio (SNR). The structural and orientational changes during vesicle’s fusion were monitored with MTR-IR. MTR-IR shows superiority over other infrared approaches for ultrathin films on standard silicon wafers in view of its economy and high sensitivity. Both MTR-IR and AFM results were consistent with each other and they provided more information for understanding the self-assembling procedure of SLBs.

Guo, Peng-Feng; Huang, Wen-Yi; Liu, Hong-Bo; Xiao, Shou-Jun

2009-01-01

234

Severe Arterial Thrombophilia Associated With a Homozygous MTHFR Gene Mutation (A1298C) in a Young Man With Klinefelter Syndrome  

Microsoft Academic Search

Klinefelter syndrome (KS) is the most common sex chromosome disorder in men. It may be associated with an increased risk for venous thrombosis and thromboembolism, which is partially explained by hypofibrinolysis due to androgen deficiency. Additional genetic or acquired thrombophilic states have been shown in KS patients complicated with venous thrombosis as isolated case reports. Arterial thrombotic events had not

Mustafa Ozbek; M. Akif Öztürk; Kemal Ureten; Ozcan Ceneli; Mehmet Erdogan; Ibrahim C. Haznedaroglu

2008-01-01

235

MTHFR A1298C polymorphism is associated with cardiovascular risk in end stage renal disease in North Indians  

Microsoft Academic Search

The methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has been shown to be associated with cardiovascular\\u000a disease and in patients with end-stage renal disease (ESRD). However, the relationship between MTHFR polymorphisms and cardiovascular\\u000a disease (CVD) in patients on hemodialysis has not been examined. The aim of this study was to assess the association of polymorphisms\\u000a of MTHFR gene with homocysteine (Hcy)

Aruna Poduri; Debabrata Mukherjee; Kamal Sud; Harbir Singh Kohli; Vinay Sakhuja; Madhu Khullar

2008-01-01

236

No association between MTHFR A1298C and MTRR A66G polymorphisms, and MS in an Australian cohort  

Microsoft Academic Search

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier

A. L. Szvetko; J. Fowdar; J. Nelson; N. Colson; L. Tajouri; P. A. Csurhes; M. P. Pender; L. R. Griffiths

2007-01-01

237

C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation  

Microsoft Academic Search

Pharmacogenetics represents an exciting, new promising tool for the individualisation of therapy. Several genetic polymorphisms and haplotypes have been considered in an attempt to optimise therapy with specific drugs but, up to now, their clinical applications remain limited.5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme of one-carbon metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Two common non-synonymous variants, the C677T

Elena De Mattia; Giuseppe Toffoli

2009-01-01

238

Prevalence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Taiwanese patients with Type 2 diabetic mellitus  

Microsoft Academic Search

ObjectivesDeficiency and\\/or decreased activity of methyltetrahydrofolate reductase (MTHFR) resulted from MTHFR variants are associated with hyperhomocysteinemia, an independent risk factor for vasculopathies in diabetic patients. The aim of this study was to examine MTHFR genotypes between healthy and type 2 diabetes mellitus (T2DM) subjects.

Yih-Hsin Chang; Wen-Mei Fu; Yu-Hui Wu; Chih-Jung Yeh; Chien-Ning Huang; Ming-Yuh Shiau

239

Mutagenesis of the C1 oxidation pathway in Methanosarcina barkeri: new insights into the Mtr/Mer bypass pathway.  

PubMed

A series of Methanosarcina barkeri mutants lacking the genes encoding the enzymes involved in the C1 oxidation/reduction pathway were constructed. Mutants lacking the methyl-tetrahydromethanopterin (H4MPT):coenzyme M (CoM) methyltransferase-encoding operon (delta mtr), the methylene-H4MPT reductase-encoding gene (delta mer), the methylene-H4MPT dehydrogenase-encoding gene (delta mtd), and the formyl-methanofuran:H4MPT formyl-transferase-encoding gene (delta ftr) all failed to grow using either methanol or H2/CO2 as a growth substrate, indicating that there is an absolute requirement for the C1 oxidation/reduction pathway for hydrogenotrophic and methylotrophic methanogenesis. The mutants also failed to grow on acetate, and we suggest that this was due to an inability to generate the reducing equivalents needed for biosynthetic reactions. Despite their lack of growth on methanol, the delta mtr and delta mer mutants were capable of producing methane from this substrate, whereas the delta mtd and delta ftr mutants were not. Thus, there is an Mtr/Mer bypass pathway that allows oxidation of methanol to the level of methylene-H4MPT in M. barkeri. The data further suggested that formaldehyde may be an intermediate in this bypass; however, no methanol dehydrogenase activity was found in delta mtr cell extracts, nor was there an obligate role for the formaldehyde-activating enzyme (Fae), which has been shown to catalyze the condensation of formaldehyde and H4MPT in vitro. Both the delta mer and delta mtr mutants were able to grow on a combination of methanol plus acetate, but they did so by metabolic pathways that are clearly distinct from each other and from previously characterized methanogenic pathways. PMID:18178739

Welander, Paula V; Metcalf, William W

2008-01-04

240

Influence of Combined Methionine Synthase (MTR 2756A > G) and Methylenetetrahydrofolate Reductase (MTHFR 677C > T) Polymorphisms to Plasma Homocysteine Levels in Korean Patients with Ischemic Stroke  

PubMed Central

Purpose Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case-control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. Materials and Methods DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p = 0.04 for MTR, p = 0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p = 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p = 0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p = 0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. Conclusion The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.

Kim, Ok Joon; Hong, Sun Pyo; Ahn, Jung Yong; Hong, Seung Ho; Hwang, Tae Sun; Kim, Soo Ok; Yoo, Wangdon; Oh, Doyeun

2007-01-01

241

Isolation of a High-Affinity Functional Protein Complex between OmcA and MtrC: Two Outer Membrane Decaheme c-type Cytochromes of Shewanella oneidensis MR-1  

SciTech Connect

SUMMARY Shewanella oneidensis MR-1 is a facultatively anaerobic bacterium that is capable of using insoluble oxidized metals, such as manganese [Mn(III, IV)] and iron [Fe(III)] oxides and oxyhydroxides, as terminal electron acceptors during anaerobic respiration. The ability of S. oneidensis MR-1 to reduce oxidized Mn and/or Fe has previously been linked to OmcA and MtrC: two decaheme c-type cytochromes that are localized to the outer membrane. To investigate how the electron transport proteins OmcA and MtrC are organized, we expressed and purified recombinant OmcA and MtrC from wild type S. oneidensis MR-1 as well as a mutant that lacked OmcA and MtrC (?omcA/mtrC). After purification to the nearly electrophoretic homogeneity from the ?omcA/mtrC mutant, the recombinant OmcA and MtrC exhibited the characteristics of c-type cytochromes, and each of their polypeptides was confirmed to contain 10 hemes. When purified from wild type cells, endogenous MtrC or OmcA was always co-purified with recombinant OmcA or MtrC, respectively. Fluorescence polarization experiment showed that recombinant OmcA bound to the FlAsH-labeled MtrC with a dissociation constant of 7 ×10-7 M. The purified recombinant OmcA or MtrC alone displayed intrinsic ferric reductase activity with NADH used as an electron donor. Ferric reductase specific activity increased by 35 to 41% when nearly equimolar concentrations of OmcA and MtrC were assayed relative to the two proteins assayed independently. These results demonstrate that OmcA and MtrC directly interact with each other to form a stable complex with high ferric reductase activity.

Shi, Liang; Chen, Baowei; Wang, Zheming; Elias, Dwayne A.; Mayer, M. Uljana; Gorby, Yuri A.; Ni, Shuisong; Lower, Brian H.; Kennedy, David W.; Wunschel, David S.; Mottaz, Heather M.; Marshall, Matthew J.; Hill, Eric A.; Beliaev, Alex S.; Zachara, John M.; Fredrickson, Jim K.; Squier, Thomas C.

2006-07-01

242

Direct Involvement of Type II Secretion System in Extracellular Translocation of Shewanella Oneidensis Outer Membrane Cytochromes MtrC and OmcA  

SciTech Connect

Outer membrane decaheme c-type cytochromes MtrC and OmcA of Shewanella oneidensis MR-1 are extracellular lipoproteins important for dissimilatory reduction of solid metal (hydr)oxides during anaerobic respiration. To investigate the roles of type II secretion system (T2S) in translocation of MtrC and OmcA across outer membrane, we measured the effects of deleting two T2S genes, gspD and gspG, on the secretion of MtrC and OmcA when cells were grown under anaerobic conditions. Deletion of gspD or gspG resulted in slightly yellowish supernatants, different from the pink supernatant of wild type (wt). Comparative proteomic analyses revealed that, although MtrC, OmcA and NrfA, a periplasmic nitrite reductase, were present the supernatants of wt and ?gspD mutant, their peptides counts were much lower in ?gspD than in wt. Subsequent analyses with heme-staining and Western blot not only confirmed that deletion of gspD or gspG reduced the abundances of MtrC and OmcA in the supernatants, but also revealed that the deletions consequently increased their abundances inside the cells. Complementation of ?gspG mutant with functional GspG could reverse the effects of deleting gspG on the colors of the supernatants and the abundances of MtrC and OmcA. In contrast, Western results showed that the abundance of NrfA was reduced in the supernatant and the cells of ?gspD mutant, suggesting that reduced NrfA in the periplasm, where MtrC and OmcA were accumulated, contributed to its reduction in the supernatant. Thus, our results demonstrate at the first time that T2S facilitates translocation of MtrC and OmcA across outer membrane.

Shi, Liang; Deng, Shuang; Marshall, Matthew J.; Wang, Zheming; Kennedy, David W.; Dohnalkova, Alice; Mottaz, Heather M.; Hill, Eric A.; Gorby, Yuri A.; Beliaev, Alex S.; Richardson, David J.; Zachara, John M.; Fredrickson, Jim K.

2008-08-01

243

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors  

SciTech Connect

Abstract MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately *500 mV (vs. the standard hydrogen electrode). Across this potential window the UV– vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled lowspin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate.

Hartshorne, Robert S.; Jepson, Brian N.; Clarke, Thomas A.; Field, Sarah J.; Fredrickson, Jim K.; Zachara, John M.; Shi, Liang; Butt, Julea N.; Richardson, David

2007-09-04

244

MTR 2756 A > G polymorphism is associated with the risk of systemic lupus erythematosus in the Polish population.  

PubMed

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overexpression of cytokines and T cell accessory molecules, which is due to a reduction of DNA regulatory region methylation in T cells. It has been shown that polymorphic variants of genes encoding key enzymes of folate and methionine metabolism may have an effect on DNA methylation. Therefore, in patients with SLE (n = 106) and controls (n = 141) we examined the distribution of polymorphisms of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR). We found that MTR 2756AG (919DG) or GG (919GG) genotype exhibited 2.005-fold increased risk of SLE (95% CI = 1.177-3.416, P = 0.0146). However, MTHFR 677C > T (A222V) and MTHFD1 1958G > A (R653Q) allele and genotype frequencies did not exhibit statistical differences between SLE patients and controls. Since MTR is located on 1q43, our findings confirm the significance of the role of 1q region and the methyl cycle in etiopathogenesis of SLE. PMID:17664238

Burzynski, M; Duriagin, S; Mostowska, M; Wudarski, M; Chwalinska-Sadowska, H; Jagodzinski, P P

2007-01-01

245

Electrochemical interaction of Shewanella oneidensis MR-1 and its outer membrane cytochromes OmcA and MtrC with hematite electrodes  

NASA Astrophysics Data System (ADS)

Bacterial metal reduction is an important biogeochemical process in anaerobic environments. An understanding of electron transfer pathways from dissimilatory metal-reducing bacteria (DMRB) to solid phase metal (hydr)oxides is important for understanding metal redox cycling in soils and sediments, for utilizing DMRB in bioremedation, and for developing technologies such as microbial fuel cells. Here we hypothesize that the outer membrane cytochromes OmcA and MtrC from Shewanella oneidensis MR-1 are the only terminal reductases capable of direct electron transfer to a hematite working electrode. Cyclic voltammetry (CV) was used to study electron transfer between hematite electrodes and protein films, S. oneidensis MR-1 wild-type cell suspensions, and cytochrome deletion mutants. After controlling for hematite electrode dissolution at negative potential, the midpoint potentials of adsorbed OmcA and MtrC were measured (-201 mV and -163 mV vs. Ag/AgCl, respectively). Cell suspensions of wild-type MR-1, deletion mutants deficient in OmcA (? omcA), MtrC (? mtrC), and both OmcA and MtrC (? mtrC-? omcA) were also studied; voltammograms for ? mtrC-? omcA were indistinguishable from the control. When the control was subtracted from the single deletion mutant voltammograms, redox peaks were consistent with the present cytochrome (i.e., ? omcA consistent with MtrC and ? mtrC consistent with OmcA). The results indicate that OmcA and MtrC are capable of direct electron exchange with hematite electrodes, consistent with a role as terminal reductases in the S. oneidensis MR-1 anaerobic respiratory pathway involving ferric minerals. There was no evidence for other terminal reductases operating under the conditions investigated. A Marcus-based approach to electron transfer kinetics indicated that the rate constant for electron transfer ket varies from 0.025 s -1 in the absence of a barrier to 63.5 s -1 with a 0.2 eV barrier.

Meitl, Leisa A.; Eggleston, Carrick M.; Colberg, Patricia J. S.; Khare, Nidhi; Reardon, Catherine L.; Shi, Liang

2009-09-01

246

Enhancement of the dissolution of albendazole from pellets using MTR technique  

PubMed Central

Albendazole (ABZ), a broad-spectrum anthelmintic agent, is poorly absorbed after oral administration due to its low aqueous solubility. The aim of this study was to improve albendazole dissolution rate by formulating avicel pellets loaded with 10% w/w drug using extrusion/spheronization technique. In addition the wet masses were characterized by mix torque rheometry (MTR) prior to pelletization process. Different additives (i.e., lactose, Tween 80 and low molecular weight chitosan) were formulated with avicel to enhance the dissolution rate of ABZ from the produced pellets. Moreover, mix torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The produced pellets were characterized for their ABZ content, particle size, particle shape, dissolution profile and thermal behaviors. The maximum consistencies (the peak torques) of the wet granules were obtained using 0.667–1.333 ml/g of water or water containing surfactant. Also, the produced pellets have size range from 1036 to 1246 ?m. The calculated drug RDR30 for 10%, 30% and 50% lactose concentrations were 1.08, 1.08 and 2.03, respectively, while that calculated for 10%, 30% and 50% w/w chitosan concentrations were 1.71, 3.62 and 3.62, respectively. The results revealed also that increasing the weight ratio of lactose and chitosan was accompanied by a significant reduction of the peak torque magnitude and this was accompanied by an enhanced ABZ dissolution rate.

Ibrahim, Mohamed A.; Al-Anazi, Fars K.

2012-01-01

247

Periplasmic Electron Transfer via the c-Type Cytochromes MtrA and FccA of Shewanella oneidensis MR-1 ?  

PubMed Central

Dissimilatory microbial reduction of insoluble Fe(III) oxides is a geochemically and ecologically important process which involves the transfer of cellular, respiratory electrons from the cytoplasmic membrane to insoluble, extracellular, mineral-phase electron acceptors. In this paper evidence is provided for the function of the periplasmic fumarate reductase FccA and the decaheme c-type cytochrome MtrA in periplasmic electron transfer reactions in the gammaproteobacterium Shewanella oneidensis. Both proteins are abundant in the periplasm of ferric citrate-reducing S. oneidensis cells. In vitro fumarate reductase FccA and c-type cytochrome MtrA were reduced by the cytoplasmic membrane-bound protein CymA. Electron transfer between CymA and MtrA was 1.4-fold faster than the CymA-catalyzed reduction of FccA. Further experiments showing a bidirectional electron transfer between FccA and MtrA provided evidence for an electron transfer network in the periplasmic space of S. oneidensis. Hence, FccA could function in both the electron transport to fumarate and via MtrA to mineral-phase Fe(III). Growth experiments with a ?fccA deletion mutant suggest a role of FccA as a transient electron storage protein.

Schuetz, Bjoern; Schicklberger, Marcus; Kuermann, Johannes; Spormann, Alfred M.; Gescher, Johannes

2009-01-01

248

Periplasmic electron transfer via the c-type cytochromes MtrA and FccA of Shewanella oneidensis MR-1.  

PubMed

Dissimilatory microbial reduction of insoluble Fe(III) oxides is a geochemically and ecologically important process which involves the transfer of cellular, respiratory electrons from the cytoplasmic membrane to insoluble, extracellular, mineral-phase electron acceptors. In this paper evidence is provided for the function of the periplasmic fumarate reductase FccA and the decaheme c-type cytochrome MtrA in periplasmic electron transfer reactions in the gammaproteobacterium Shewanella oneidensis. Both proteins are abundant in the periplasm of ferric citrate-reducing S. oneidensis cells. In vitro fumarate reductase FccA and c-type cytochrome MtrA were reduced by the cytoplasmic membrane-bound protein CymA. Electron transfer between CymA and MtrA was 1.4-fold faster than the CymA-catalyzed reduction of FccA. Further experiments showing a bidirectional electron transfer between FccA and MtrA provided evidence for an electron transfer network in the periplasmic space of S. oneidensis. Hence, FccA could function in both the electron transport to fumarate and via MtrA to mineral-phase Fe(III). Growth experiments with a DeltafccA deletion mutant suggest a role of FccA as a transient electron storage protein. PMID:19837833

Schuetz, Bjoern; Schicklberger, Marcus; Kuermann, Johannes; Spormann, Alfred M; Gescher, Johannes

2009-10-16

249

Genetic interactions suggest multiple distinct roles of the arch and core helicase domains of Mtr4 in Rrp6 and exosome function.  

PubMed

The RNA exosome is responsible for a wide variety of RNA processing and degradation reactions. The activity and specificity of the RNA exosome is thought to be controlled by a number of cofactors. Mtr4 is an essential RNA-dependent adenosine triphosphatase that is required for all of the nuclear functions of the RNA exosome. The crystal structure of Mtr4 uncovered a domain that is conserved in the RNA exosome cofactors Mtr4 and Ski2 but not in other helicases, suggesting it has an important role related to exosome activation. Rrp6 provides the nuclear exosome with one of its three nuclease activities, and previous findings suggested that the arch domain is specifically required for Rrp6 functions. Here, we report that the genetic interactions between the arch domain of Mtr4 and Rrp6 cannot be explained by the arch domain solely acting in Rrp6-dependent processing reactions. Specifically, we show that the arch domain is not required for all Rrp6 functions, and that the arch domain also functions independently of Rrp6. Finally, we show that the arch domain of Ski2, the cytoplasmic counterpart of Mtr4, is required for Ski2's function, thereby confirming that the arch domains of these cofactors function independently of Rrp6. PMID:23143101

Klauer, A Alejandra; van Hoof, Ambro

2012-11-09

250

Genetic interactions suggest multiple distinct roles of the arch and core helicase domains of Mtr4 in Rrp6 and exosome function  

PubMed Central

The RNA exosome is responsible for a wide variety of RNA processing and degradation reactions. The activity and specificity of the RNA exosome is thought to be controlled by a number of cofactors. Mtr4 is an essential RNA-dependent adenosine triphosphatase that is required for all of the nuclear functions of the RNA exosome. The crystal structure of Mtr4 uncovered a domain that is conserved in the RNA exosome cofactors Mtr4 and Ski2 but not in other helicases, suggesting it has an important role related to exosome activation. Rrp6 provides the nuclear exosome with one of its three nuclease activities, and previous findings suggested that the arch domain is specifically required for Rrp6 functions. Here, we report that the genetic interactions between the arch domain of Mtr4 and Rrp6 cannot be explained by the arch domain solely acting in Rrp6-dependent processing reactions. Specifically, we show that the arch domain is not required for all Rrp6 functions, and that the arch domain also functions independently of Rrp6. Finally, we show that the arch domain of Ski2, the cytoplasmic counterpart of Mtr4, is required for Ski2’s function, thereby confirming that the arch domains of these cofactors function independently of Rrp6.

Klauer, A. Alejandra; van Hoof, Ambro

2013-01-01

251

Missense mutations that alter the DNA-binding domain of the MtrR protein occur frequently in rectal isolates of Neisseria gonorrhoeae that are resistant to faecal lipids.  

PubMed

Resistance of Neisseria gonorrhoeae to structurally diverse hydrophobic agents (HAs) has been associated with missense or deletion mutations in the mtrR (multiple transferable resistance Regulator) gene of laboratory-derived strains but their prevalence in clinical isolates was heretofore unknown. Since faecal lipids provide strong selective pressure for the emergence of variants resistant to HAs (HAR), the nucleotide sequence of the mtrR gene from rectal isolates of N. gonorrhoeae, which displayed different levels of HAR, was determined. Compared to the mtrR gene possessed by the HA-sensitive strain FA19, each clinical isolate contained mutations in the coding and/or promoter regions of their mtrR gene. A missense mutation in codon 45 (Gly-45 to Asp) was the most common mutation found in the strains studied and impacted the structure of the helix-turn-helix domain of the MtrR protein thought to be important in DNA-binding activity. Two clinical isolates bearing a missense mutation in codon 45 also contained a single basepair deletion in a 13 bp inverted sequence positioned within the mtrR promoter region. Introduction of mtrR sequences amplified from the clinical isolates into strain FA19 revealed that acquisition of the single basepair deletion was correlated with high level HAR while mutations in the mtrR-coding region provided for an intermediate level of HAR. PMID:7773394

Shafer, W M; Balthazar, J T; Hagman, K E; Morse, S A

1995-04-01

252

Deletion of mtrC in Haemophilus ducreyi Increases Sensitivity to Human Antimicrobial Peptides and Activates the CpxRA Regulon ?  

PubMed Central

Haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, ?-defensins, and ?-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance in H. ducreyi. We found a proton motive force-dependent effect on H. ducreyi's resistance to LL-37 and ?-defensin HBD-3, but not ?-defensin HNP-2. Deletion of the membrane fusion protein MtrC rendered H. ducreyi more sensitive to LL-37 and human ?-defensins but had relatively little effect on ?-defensin resistance. The mtrC mutant 35000HPmtrC exhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type by trans-complementation with mtrC. Similar phenotypes were reported in a cpxA mutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. A cpxR mutant had wild-type levels of antimicrobial peptide resistance; a cpxA mutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrC was more sensitive than the cpxA mutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrC had lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human ?-defensins. This is the first report of a ?-defensin resistance mechanism in H. ducreyi and shows that LL-37 resistance in H. ducreyi is multifactorial.

Rinker, Sherri D.; Trombley, Michael P.; Gu, Xiaoping; Fortney, Kate R.; Bauer, Margaret E.

2011-01-01

253

Specific Bonds between an Iron Oxide Surface and Outer Membrane Cytochromes MtrC and OmcA from Shewanella oneidensis MR-1  

SciTech Connect

Shewanella oneidensis MR-1 is purported to express outer membrane cytochromes (e.g., MtrC and OmcA) that transfer electrons directly to Fe(III) in a mineral during anaerobic respiration.  A prerequisite for this type of reaction would be the formation of a stable bond between a cytochrome and an iron oxide surface.  Atomic force microscopy (AFM) was used to detect whether a specific bond forms between a hematite (Fe2O3) thin film, created with oxygen plasma assisted molecular beam epitaxy (MBE), and recombinant MtrC or OmcA molecules coupled to gold substrates.  Force spectra displayed a unique force signature indicative of a specific bond between each cytochrome and the hematite surface.  The strength of the OmcA-hematite bond was approximately twice as strong as the MtrC-hematite bond, but direct binding to hematite was twice as favorable for MtrC.  Reversible folding/unfolding reactions were observed for mechanically denatured MtrC molecules bound to hematite.  The force measurements for the hematite-cytochrome pairs were compared to spectra collected between an iron oxide and S. oneidensis under anaerobic conditions.  There is a strong correlation between the whole cell and pure protein force spectra suggesting that the unique binding attributes of each cytochrome complement one another and allow both MtrC and OmcA to play a prominent role in the transfer of electrons to Fe(III) in minerals.  Finally, by comparing the magnitude of binding force for the whole cell vs. pure protein data, we were able to estimate that a single bacterium of S. oneidensis (2 x 0.5 ?m) expresses ~104 cytochromes on its outer surface. 

Lower, Brian H.; Shi, Liang; Yongsunthon, Ruchirej; Droubay, Timothy; Mccready, David E.; Lower, Steven

2007-07-31

254

Characterization of Axial and Proximal Histidine Mutations of the Decaheme Cytochrome MtrA from Shewanella sp. Strain ANA-3 and Implications for the Electron Transport System  

PubMed Central

Extracellular respiration of solid-phase electron acceptors in some microorganisms requires a complex chain of multiheme c-type cytochromes that span the inner and outer membranes. In Shewanella species, MtrA, an ?35-kDa periplasmic decaheme c-type cytochrome, is an essential component for extracellular respiration of iron(III). The exact mechanism of electron transport has not yet been resolved, but the arrangement of the polypeptide chain may have a strong influence on the capability of the MtrA cytochrome to transport electrons. The iron hemes of MtrA are bound to its polypeptide chain via proximal (CXXCH) and distal histidine residues. In this study, we show the effects of mutating histidine residues of MtrA to arginine on protein expression and extracellular respiration using Shewanella sp. strain ANA-3 as a model organism. Individual mutations to six out of nine proximal histidines in CXXCH of MtrA led to decreased protein expression. However, distal histidine mutations resulted in various degrees of protein expression. In addition, the effects of histidine mutations on extracellular respiration were tested using ferrihydrite and current production in microbial fuel cells. These results show that proximal histidine mutants were unable to reduce ferrihydrite. Mutations to the distal histidine residues resulted in various degrees of ferrihydrite reduction. These findings indicate that mutations to the proximal histidine residues affect MtrA expression, leading to loss of extracellular respiration ability. In contrast, mutations to the distal histidine residues are less detrimental to protein expression, and extracellular respiration can proceed.

Qian, Fang; Zhang, Alissa; Bondarev, Sergey; Welch, Angel; Thelen, Michael P.

2012-01-01

255

Delay Discounting and Frontostriatal Fiber Tracts: A Combined DTI and MTR Study on Impulsive Choices in Healthy Young Adults  

PubMed Central

Delay discounting, a measure of impulsive choice, has been associated with decreased control of the prefrontal cortex over striatum responses. The anatomical connectivity between both brain regions in delaying gratification remains unknown. Here, we investigate whether the quality of frontostriatal (FS) white matter tracts can predict individual differences in delay-discounting behavior. We use tract-based diffusion tensor imaging and magnetization transfer imaging to measure the microstructural properties of FS fiber tracts in 40 healthy young adults (from 18 to 25 years). We additionally explored whether internal sex hormone levels affect the integrity of FS tracts, based on the hypothesis that sex hormones modulate axonal density within prefrontal dopaminergic circuits. We calculated fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusivity, radial diffusivity (RD), and magnetization transfer ratio (MTR), a putative measure of myelination, for the FS tract. Results showed that lower integrity within the FS tract (higher MD and RD and lower FA), predicts faster discounting in both sexes. MTR was unrelated to delay-discounting performance. In addition, testosterone levels in males were associated with a lower integrity (higher RD) within the FS tract. Our study provides support for the hypothesis that enhanced structural integrity of white matter fiber bundles between prefrontal and striatal brain areas is associated with better impulse control.

Peper, Jiska S.; Mandl, Rene C.W.; Braams, Barbara R.; de Water, Erik; Heijboer, Annemieke C.; Koolschijn, P. Cedric M.P.; Crone, Eveline A.

2013-01-01

256

In Vivo Identification of the Outer Membrane Protein OmcA-MtrC Interaction Network in Shewanella oneidensis MR-1 Cells Using Novel Hydrophobic Chemical Cross-Linkers  

SciTech Connect

Outer membrane (OM) cytochromes OmcA (SO1779) and MtrC (SO1778) are the integral components of electron transfer used by Shewanella oneidensis for anaerobic respiration of metal (hydr)oxides. Here the OmcA-MtrC interaction was identified in vivo using a novel hydrophobic chemical cross-linker (MRN) combined with immunoprecipitation techniques. In addition, identification of other OM proteins from the cross-linked complexes allows first visualization of the OmcA-MtrC interaction network. Further experiments on omcA and mtrC mutant cells showed OmcA plays a central role in the network interaction. For comparison, two commercial cross-linkers were also used in parallel and both resulted in fewer OM protein identifications, indicating the superior properties of MRN for identification of membrane protein interactions. Finally, comparison experiments of in vivo cross-linking and cell lysate cross-linking resulted in significantly different protein interaction data, demonstrating the importance of in vivo cross-linking for study of protein-protein interactions in cells.

Zhang, Haizhen; Tang, Xiaoting; Munske, Gerhard R.; Zakharova, Natalia L.; Yang, Li; Zheng, Chunxiang; Wolff, Meagan A.; Tolic, Nikola; Anderson, Gordon A.; Shi, Liang; Marshall, Matthew J.; Fredrickson, Jim K.; Bruce, James E.

2008-04-01

257

Assurance of Fabrication Technology for MTR Fuel Elements with Low-Enriched Uranium in a First LEU Core of a West German Research Reactor, Project 12. Final Report.  

National Technical Information Service (NTIS)

R and D work is reported that accompanied the process engineering work for the fabrication of MTR fuel elements with low U-235 enrichment, results to be used for the design of the series production process. The fabrication of the fuel elements for a first...

K. H. Koch M. Mueller

1988-01-01

258

C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing  

PubMed Central

The exosome is a complex of 3?–5? exoribonucleases and RNA-binding proteins, which is involved in processing or degradation of different classes of RNA. Previously, the characterization of purified exosome complexes from yeast and human cells suggested that C1D and KIAA0052/hMtr4p are associated with the exosome and thus might regulate its functional activities. Subcellular localization experiments demonstrated that C1D and KIAA0052/hMtr4p co-localize with exosome subunit PM/Scl-100 in the nucleoli of HEp-2 cells. Additionally, the nucleolar accumulation of C1D appeared to be dependent on PM/Scl-100. Protein–protein interaction studies showed that C1D binds to PM/Scl-100, whereas KIAA0052/hMtr4p was found to interact with MPP6, a previously identified exosome-associated protein. Moreover, we demonstrate that C1D, MPP6 and PM/Scl-100 form a stable trimeric complex in vitro. Knock-down of C1D, MPP6 and KIAA0052/hMtr4p by RNAi resulted in the accumulation of 3?-extended 5.8S rRNA precursors, showing that these proteins are required for rRNA processing. Interestingly, C1D appeared to contain RNA-binding activity with a potential preference for structured RNAs. Taken together, our results are consistent with a role for the exosome-associated proteins C1D, MPP6 and KIAA052/hMtr4p in the recruitment of the exosome to pre-rRNA to mediate the 3? end processing of the 5.8S rRNA.

Schilders, Geurt; van Dijk, Erwin; Pruijn, Ger J.M.

2007-01-01

259

Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma.  

PubMed

Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R-->3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43-0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. PMID:17546637

Kim, Hee Nam; Kim, Yeo-Kyeoung; Lee, Il-Kwon; Lee, Je-Jung; Yang, Deok-Hwan; Park, Kyeong-Soo; Choi, Jin-Su; Park, Moo Rim; Jo, Deog Yeon; Kim, Hyeoung-Joon

2007-09-01

260

Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population.  

PubMed

Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase ( MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggested that a defective methionine synthase ( MS) enzyme could be a critical defect in folate-related NTDs. An A-to-G transition at bp 2756 on the MS gene has also been reported. In this case-control study, we studied the frequencies of these two polymorphisms in 203 Italian probands with non-syndromic NTDs: 98 mothers, 67 fathers, and 210 control individuals. Although the A1298C polymorphism is common in the Italian population (0.25), the allelic frequency was significantly higher among NTD cases and their parents. Heterozygous patients and mothers have an odds ratio (OR) of 1.98 and 2.11, respectively. The risk associated with the 1298CC genotype was higher for cases (OR = 3.67), for fathers (OR = 3.28), and, above all, for mothers (OR = 6.23). The prevalence of the A2756G polymorphism of the MS gene was determined (0.15). No increased prevalence of the mutated G allele was found in NTD families. This study shows that the MTHFRA1298C polymorphism is a genetic determinant for NTD risk in Italy. No association between the MSA2756G and NTD susceptibility was found. PMID:12111380

De Marco, Patrizia; Calevo, Maria Grazia; Moroni, Anna; Arata, Lorenza; Merello, Elisa; Finnell, Richard H; Zhu, Huiping; Andreussi, Luciano; Cama, Armando; Capra, Valeria

2002-01-01

261

Effect of cystathionine beta-synthase variant 844ins68bp and methylenetetrahydrofolate reductase A1298C polymorphisms in xenografts on 5FU efficacy and doubling time  

Microsoft Academic Search

The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling

Shin Sasaki; Toshiaki Watanabe; Takashi Kobunai; Hirokazu Nagawa

2006-01-01

262

Vitamin B12 Status Is Inversely Associated with Plasma Homocysteine in Young Women with C677T and\\/or A1298C Methylenetetrahydrofolate Reductase Polymorphisms1  

Microsoft Academic Search

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may negatively influence one-carbon metabolism and increase health risks in women of reproductive age. The effect of MTHFR single nucleotide polymorphisms at bp 677 and\\/or 1298 and differences in folate and vitamin B-12 status on plasma homocysteine concentration in women of reproductive age (20 -30 y; n 186) were investigated. From the multivariate regression model, homozygotes

Lynn B. Bailey; Robert L. Duhaney; David R. Maneval; Gail P. A. Kauwell; Eoin P. Quinlivan; Steven R. Davis; Aisha Cuadras; Alan D. Hutson; Jesse F. Gregory

263

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men  

Microsoft Academic Search

We performed a case–control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the\\u000a association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer\\u000a susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were\\u000a frequency-matched to the cases by age (±5 years), ethnicity, and smoking status. We also measured

Nayyer Shafiei; Shiva Safarinejad

264

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and the risk of primary Hepatocellular Carcinoma (HCC) in a Chinese population  

Microsoft Academic Search

Objectives  Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and\\u000a DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To\\u000a date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective\\u000a of this study was

Li-Na Mu; Wei Cao; Zuo-Feng Zhang; Lin Cai; Qing-Wu Jiang; Nai-Chieh You; Binh Yang Goldstein; Guo-Rong Wei; Chuan-Wei Chen; Qing-Yi Lu; Xue-Fu Zhou; Bao-Guo Ding; Jun Chang; Shun-Zhang Yu

2007-01-01

265

Exploring the Effects of Methylenetetrahydrofolate Reductase Gene Variants C677T and A1298C on the Risk of Orofacial Clefts in 261 Norwegian Case-Parent Triads  

Microsoft Academic Search

Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both been implicated in the etiology of orofacial clefts. The authors selected 261 case-parent triads (173 cases with cleft lip with or without cleft palate (CL\\/P) and 88 cases with cleft palate only (CPO)) from a Norwegian population-based study of orofacial clefts (May 1996-1998). A case-parent triad design was used to

Astanand Jugessur; Allen J. Wilcox; Rolv T. Lie; Jeffrey C. Murray; Jack A. Taylor

2003-01-01

266

Hyperhomocysteinemia and MTHFR C677T and A1298C polymorphisms are associated with chronic allograft nephropathy in renal transplant recipients  

Microsoft Academic Search

Hyperhomocysteine has been reported to be an important risk factor for the development of atherosclerosis. Identification of risk factors, such as hyperhomocysteinemia, is crucial for a better understanding of the events that lead to degenerative processes in the vascular system and for a correct understanding of the potential role of methylene-tetrahydrofolate reductase enzymes (MTHFR) to help in the treatment of

E. C. Pavarino-Bertelli; M. P. Sanches de Alvarenga; E. M. Goloni-Bertollo; M. A. S. F. Baptista; R. Haddad; N. F. Hoerh; M. N. Eberlin; M. Abbud-Filho

2004-01-01

267

Specific Bonds between an Iron Oxide Surface and Outer Membrane Cytochromes MtrC and OmcA from Shewanella oneidensis MR1  

Microsoft Academic Search

Shewanella oneidensis MR-1 is purported to express outer membrane cytochromes (e.g., MtrC and OmcA) that transfer electrons directly to Fe(III) in a mineral during anaerobic respiration.  A prerequisite for this type of reaction would be the formation of a stable bond between a cytochrome and an iron oxide surface.  Atomic force microscopy (AFM) was used to detect whether a specific

Brian H. Lower; Liang Shi; Ruchirej Yongsunthon; Timothy C. Droubay; David E. Mccready; Steven K. Lower

2007-01-01

268

Role of outer-membrane cytochromes MtrC and OmcA in the biomineralization of ferrihydrite by Shewanella oneidensis MR-1.  

PubMed

In an effort to improve the understanding of electron transfer mechanisms at the microbe-mineral interface, Shewanella oneidensis MR-1 mutants with in-frame deletions of outer-membrane cytochromes (OMCs), MtrC and OmcA, were characterized for the ability to reduce ferrihydrite (FH) using a suite of microscopic, spectroscopic, and biochemical techniques. Analysis of purified recombinant proteins demonstrated that both cytochromes undergo rapid electron exchange with FH in vitro with MtrC displaying faster transfer rates than OmcA. Immunomicroscopy with cytochrome-specific antibodies revealed that MtrC co-localizes with iron solids on the cell surface while OmcA exhibits a more diffuse distribution over the cell surface. After 3-day incubation of MR-1 with FH, pronounced reductive transformation mineral products were visible by electron microscopy. Upon further incubation, the predominant phases identified were ferrous phosphates including vivianite [Fe(3)(PO(4))(2)x8H(2)O] and a switzerite-like phase [Mn(3),Fe(3)(PO(4))(2)x7H(2)O] that were heavily colonized by MR-1 cells with surface-exposed outer-membrane cytochromes. In the absence of both MtrC and OmcA, the cells ability to reduce FH was significantly hindered and no mineral transformation products were detected. Collectively, these results highlight the importance of the outer-membrane cytochromes in the reductive transformation of FH and support a role for direct electron transfer from the OMCs at the cell surface to the mineral. PMID:20002197

Reardon, C L; Dohnalkova, A C; Nachimuthu, P; Kennedy, D W; Saffarini, D A; Arey, B W; Shi, L; Wang, Z; Moore, D; McLean, J S; Moyles, D; Marshall, M J; Zachara, J M; Fredrickson, J K; Beliaev, A S

2009-11-25

269

C1D and hMtr4p associate with the human exosome subunit PM\\/Scl-100 and are involved in pre-rRNA processing  

Microsoft Academic Search

The exosome is a complex of 30-50 exoribonucleases and RNA-binding proteins, which is involved in processing or degradation of different classes of RNA. Previously, the characterization of purified exosome complexes from yeast and human cells suggested that C1D and KIAA0052\\/hMtr4p are associated with the exosome and thus might regu- late its functional activities. Subcellular localization experiments demonstrated that C1D and

Geurt Schilders; Erwin van Dijk; Ger J. M. Pruijn

2007-01-01

270

Kinetics of Reduction of Fe(III) Complexes by Outer Membrane Cytochromes MtrC and OmcA of Shewanella oneidensis MR1  

Microsoft Academic Search

Shewanella Oneidensis MR-1 possesses up to 42 c-type cytochromes with heme content varying between 1 to as many as 37. Among them, the outer-membrane cytochromes, particularly MtrC and OmcA, are suspected to function as terminal reductases and are responsible for its enzymatic catalysis capability. So far, the mechanisms of metal reduction by these outer-membrane cytochromes are unknown. In this work,

Zheming Wang; Chongxuan Liu; Xuelin Wang; Matthew J. Marshall; John M. Zachara; Kevin M. Rosso; Michel Dupuis; James K. Fredrickson; Steve M. Heald; Liang Shi

2008-01-01

271

Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans.  

PubMed

The methylenetetrahydrofolate reductase (MTHFR), cystathione-?-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1?mol/L; p<0.05) compared to subjects harboring the MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5?mol/L, respectively). The investigated CBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene-gene interactions allude to epistatic effects. PMID:23954866

Nienaber-Rousseau, Cornelie; Ellis, Suria M; Moss, Sarah J; Melse-Boonstra, Alida; Towers, G Wayne

2013-08-14

272

MtrR Control of a Transcriptional Regulatory Pathway in Neisseria meningitidis That Influences Expression of a Gene (nadA) Encoding a Vaccine Candidate  

PubMed Central

The surface-exposed NadA adhesin produced by a subset of capsular serogroup B strains of Neisseria meningitidis is currently being considered as a vaccine candidate to prevent invasive disease caused by a hypervirulent lineage of meningococci. Levels of NadA are known to be controlled by both transcriptional regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. Herein, we confirmed the capacity of a DNA-binding protein termed FarR to negatively control nadA expression. We also found that a known transcriptional regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory impact on farR and nadA expression, especially when over-expressed. MtrR-mediated repression of nadA was found to be direct, and its binding to a target DNA sequence containing the nadA promoter influenced formation and/or stability of FarR::nadA complexes. The complexity of the multi-layered regulation of nadA uncovered during this investigation suggests that N. meningitidis modulates NadA adhesin protein levels for the purpose of interacting with host cells yet avoiding antibody directed against surface exposed epitopes.

Cloward, Jason M.; Shafer, William M.

2013-01-01

273

MtrR control of a transcriptional regulatory pathway in Neisseria meningitidis that influences expression of a gene (nadA) encoding a vaccine candidate.  

PubMed

The surface-exposed NadA adhesin produced by a subset of capsular serogroup B strains of Neisseria meningitidis is currently being considered as a vaccine candidate to prevent invasive disease caused by a hypervirulent lineage of meningococci. Levels of NadA are known to be controlled by both transcriptional regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. Herein, we confirmed the capacity of a DNA-binding protein termed FarR to negatively control nadA expression. We also found that a known transcriptional regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory impact on farR and nadA expression, especially when over-expressed. MtrR-mediated repression of nadA was found to be direct, and its binding to a target DNA sequence containing the nadA promoter influenced formation and/or stability of FarR::nadA complexes. The complexity of the multi-layered regulation of nadA uncovered during this investigation suggests that N. meningitidis modulates NadA adhesin protein levels for the purpose of interacting with host cells yet avoiding antibody directed against surface exposed epitopes. PMID:23409129

Cloward, Jason M; Shafer, William M

2013-02-08

274

Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase  

PubMed Central

Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. Early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. However, recent studies have suggested additional roles for telomerase components in transcription and the response to DNA damage. To examine these potential telomere length maintenance-independent roles of telomerase components, we examined first generation mTR?/? and mTERT?/? mice with long telomeres. We used gene expression profiling and found no genes that were differentially expressed in mTR?/? G1 mice and mTERT?/? G1 mice compared with wild-type mice. We also compared the response to DNA damage in mTR?/?G1 and mTERT?/? G1 mouse embryonic fibroblasts, and found no increase in the response to DNA damage in the absence of either telomerase component compared to wild-type. We conclude that, under physiologic conditions, neither mTR nor mTERT acts as a transcription factor or plays a role in the DNA damage response.

Vidal-Cardenas, Sofia L.; Greider, Carol W.

2010-01-01

275

Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase.  

PubMed

Telomerase, the essential enzyme that maintains telomere length, contains two core components, TERT and TR. Early studies in yeast and mouse showed that loss of telomerase leads to phenotypes only after several generations, due to telomere shortening. However, recent studies have suggested additional roles for telomerase components in transcription and the response to DNA damage. To examine these potential telomere length maintenance-independent roles of telomerase components, we examined first generation mTR(-/-) and mTERT(-/-) mice with long telomeres. We used gene expression profiling and found no genes that were differentially expressed in mTR(-/-) G1 mice and mTERT(-/-) G1 mice compared with wild-type mice. We also compared the response to DNA damage in mTR(-/-)G1 and mTERT(-/-) G1 mouse embryonic fibroblasts, and found no increase in the response to DNA damage in the absence of either telomerase component compared to wild-type. We conclude that, under physiologic conditions, neither mTR nor mTERT acts as a transcription factor or plays a role in the DNA damage response. PMID:19850716

Vidal-Cardenas, Sofia L; Greider, Carol W

2009-10-22

276

Defects in mTR stability and telomerase activity produced by the Dkc1 A353V mutation in dyskeratosis congenita are rescued by a peptide from the dyskerin TruB domain  

PubMed Central

The predominant X-linked form of Dyskeratosis congenita results from mutations in dyskerin, a protein required for ribosomal RNA modification that is also a component of the telomerase complex. We have previously found that expression of an internal fragment of dyskerin (GSE24.2) rescues telomerase activity in X-linked dyskeratosis congenita (X-DC) patient cells. Here we have generated F9 mouse cell lines expressing the most frequent mutation found in X-DC patients, A353V and investigate the effect of expressing the GSE24.2 cDNA or GSE24.2 peptide on telomerase activity, mTERT and mTR expression. Expression of GSE24.2 increases mTR and to a lesser extent mTERT RNA levels and leads to recovery of telomerase activity. Point mutations in GSE24.2 residues known to be highly conserved and crucial for the pseudouridine-synthase activity of dyskerin abolished the effect of the peptide. Recovery of telomerase activity and increase in mTERT levels were found when the GSE24.2 peptide purified from bacteria was introduced into the cells Moreover mTR stability was also rescued by transfection of the peptide GSE24.2. These data indicate that supplying GSE24.2, either from a cDNA vector, or as a peptide, can reduce the pathogenic effects of Dkc1 mutations and could form the basis of a novel therapeutic approach.

Machado-Pinilla, R; Carrillo, J.; Manguan-Garcia, C; Sastre, L; Mentzer, A; Gu, B-W; Mason, PJ; Perona, R

2013-01-01

277

Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women.  

PubMed

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n = 300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p < 0.001) in young women with CC or CT of MTHFR than with TT (10.9+/-4.7 micromol/L) (n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0+/-8.6 nmol/L) and lowest (7.6+/-1.5 micromol/L) levels, respectively, after folic acid (400 microg/day) supplementation. In the regression equation ( y= ax + b) of serum folate ( y nmol/L) plotted against mean folate intake ( x microg/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR. PMID:15044114

Hiraoka, Mami; Kato, Kumiko; Saito, Yoko; Yasuda, Kazuto; Kagawa, Yasuo

2004-04-16

278

Neisseria gonorrhoeae Isolates with Reduced Susceptibility to Cefixime and Ceftriaxone: Association with Genetic Polymorphisms in penA, mtrR, porB1b, and ponA  

Microsoft Academic Search

reduced cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequenc- ing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n 18), the MICs of cefixime and ceftriaxone ranged between 0.032 to 0.38 g\\/ml and 0.064 to 0.125 g\\/ml, respectively. These isolates were assigned

Robert Lindberg; Hans Fredlund; Robert Nicholas; Magnus Unemo

2007-01-01

279

The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study  

Microsoft Academic Search

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the

V. Dekou; P. Whincup; O. Papacosta; S. Ebrahim; L. Lennon; P. M. Ueland; H. Refsum; S. E. Humphries; V. Gudnason

2001-01-01

280

No Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort A.L. Szvetkoa, J. Fowdara, J. Nelsona, N. Colsona, L. Tajouria  

Microsoft Academic Search

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier

P. A. Csurhes; L. R. Griffiths

281

Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population  

PubMed Central

Background Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-?-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population. Methodology/Principal Findings In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [?(SE ?), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [?(SE ?), ?0.56(0.58) and ?0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was ?1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in folate and vitamin B12 deficiencies and high blood lead (p value <0.05) level. Conclusions Gene polymorphism (especially MTHFR C677T transition), folate and vitamin B12 deficiencies, male gender and high blood lead level appear to be contributing towards the development of hyperhomocysteinemia in a Pakistani population.

Yakub, Mohsin; Moti, Naushad; Parveen, Siddiqa; Chaudhry, Bushra; Azam, Iqbal; Iqbal, Mohammad Perwaiz

2012-01-01

282

Air1 Zinc Knuckles 4 and 5 and a Conserved IWRXY Motif Are Critical for the Function and Integrity of the Trf4/5-Air1/2-Mtr4 Polyadenylation (TRAMP) RNA Quality Control Complex*  

PubMed Central

In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome cofactor that recruits the exosome to degrade RNAs. Trf4/5 are poly(A) polymerases, Mtr4 is an RNA helicase, and Air1/2 are putative RNA-binding proteins that contain five CCHC zinc knuckles (ZnKs). One central question is how the TRAMP complex, especially the Air1/2 protein, recognizes its RNA substrates. To characterize the function of the Air1/2 protein, we used random mutagenesis of the AIR1/2 gene to identify residues critical for Air protein function. We identified air1-C178R and air2-C167R alleles encoding air1/2 mutant proteins with a substitution in the second cysteine of ZnK5. Mutagenesis of the second cysteine in AIR1/2 ZnK1–5 reveals that Air1/2 ZnK4 and -5 are critical for Air protein function in vivo. In addition, we find that the level of CUT, NEL025c, in air1 ZnK1–5 mutants is stabilized, particularly in air1 ZnK4, suggesting a role for Air1 ZnK4 in the degradation of CUTs. We also find that Air1/2 ZnK4 and -5 are critical for Trf4 interaction and that the Air1-Trf4 interaction and Air1 level are critical for TRAMP complex integrity. We identify a conserved IWRXY motif in the Air1 ZnK4-5 linker that is important for Trf4 interaction. We also find that hZCCHC7, a putative human orthologue of Air1 that contains the IWRXY motif, localizes to the nucleolus in human cells and interacts with both mammalian Trf4 orthologues, PAPD5 and PAPD7 (PAP-associated domain containing 5 and 7), suggesting that hZCCHC7 is the Air component of a human TRAMP complex.

Fasken, Milo B.; Leung, Sara W.; Banerjee, Ayan; Kodani, Maja O.; Chavez, Ramiro; Bowman, Elizabeth A.; Purohit, Meghan K.; Rubinson, Max E.; Rubinson, Emily H.; Corbett, Anita H.

2011-01-01

283

Effects of methionine synthase and methylenetetrahydrofolate reductase gene polymorphisms on markers of one-carbon metabolism.  

PubMed

Genetic and nutritional factors play a role in determining the functionality of the one-carbon (1C) metabolism cycle, a network of biochemical reactions critical to intracellular processes. Genes encoding enzymes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) may determine biomarkers of the cycle including homocysteine (HCY), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). MTHFR C677T is an established genetic determinant of HCY but less is known of its effect on SAM and SAH. Conversely, the relationship between MTR A2756G and HCY remains inconclusive, and its effect on SAM and SAH has only been previously investigated in a female-specific population. Folate and vitamin B12 are essential substrate and cofactor of 1C metabolism; thus, consideration of gene-nutrient interactions may clarify the role of genetic determinants of HCY, SAM and SAH. This cross-sectional study included 570 healthy volunteers from Kingston, Ontario, Ottawa, Ontario and Halifax, Nova Scotia, Canada. Least squares regression was used to examine the effects of MTR and MTHFR polymorphisms on plasma HCY, SAM and SAH concentrations; gene-gene and gene-nutrient interactions were considered with the inclusion of cross-products in the model. Main effects of MTR and MTHFR polymorphisms on HCY concentrations were observed; however, no gene-gene or gene-nutrient interactions were found. No association was observed for SAM. For SAH, interactions between MTR and MTHFR polymorphisms, and MTHFR polymorphism and serum folate were found. The findings of this research provide evidence that HCY and SAH, biomarkers of 1C metabolism, are influenced by genetic and nutritional factors and their interactions. PMID:24101362

Ho, Vikki; Massey, Thomas E; King, Will D

2013-10-08

284

Genetic variants of methyl metabolizing enzymes and epigenetic regulators: associations with promoter CpG island hypermethylation in colorectal cancer.  

PubMed

Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of folate metabolizing enzymes (MTHFR, MTR, and MTRR), DNA methyltransferase DNMT3b, and histone methyltransferases (EHMT1, EHMT2, and PRDM2), with colorectal cancers, with or without the CpG island methylator phenotype (CIMP), MLH1 hypermethylation, or microsatellite instability. Incidence rate ratios were calculated in case-cohort analyses, with common homozygotes as reference, among 659 cases and 1,736 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852). Men with the MTHFR 677TT genotype were at decreased colorectal cancer risk (incidence rate ratio, 0.49; P = 0.01), but the T allele was associated with increased risk in women (incidence rate ratio, 1.39; P = 0.02). The MTR 2756GG genotype was associated with increased colorectal cancer risk (incidence rate ratio, 1.58; P = 0.04), and inverse associations were observed among women carrying DNMT3b C-->T (rs406193; incidence rate ratio, 0.72; P = 0.04) or EHMT2 G-->A (rs535586; incidence rate ratio, 0.76; P = 0.05) polymorphisms. Although significantly correlated (P < 0.001), only 41.5% and 33.3% of CIMP tumors harbored MLH1 hypermethylation or microsatellite instability, respectively. We observed inverse associations between MTR A2756G and CIMP among men (incidence rate ratio, 0.58; P = 0.04), and between MTRR A66G and MLH1 hypermethylation among women (incidence rate ratio, 0.55; P = 0.02). In conclusion, MTHFR, MTR, DNMT3b, and EHMT2 polymorphisms are associated with colorectal cancer, and rare variants of MTR and MTRR may reduce promoter hypermethylation. The incomplete overlap between CIMP, MLH1 hypermethylation, and microsatellite instability indicates that these related "methylation phenotypes" may not be similar and should be investigated separately. PMID:19843671

de Vogel, Stefan; Wouters, Kim A D; Gottschalk, Ralph W H; van Schooten, Frederik J; de Goeij, Anton F P M; de Bruïne, Adriaan P; Goldbohm, Royle A; van den Brandt, Piet A; Weijenberg, Matty P; van Engeland, Manon

2009-10-20

285

Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.  

PubMed

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation. PMID:15159311

Gemmati, Donato; Ongaro, Alessia; Scapoli, Gian L; Della Porta, Matteo; Tognazzo, Silvia; Serino, Maria L; Di Bona, Eros; Rodeghiero, Francesco; Gilli, Giuseppe; Reverberi, Roberto; Caruso, Angelo; Pasello, Michela; Pellati, Agnese; De Mattei, Monica

2004-05-01

286

Epistatic interactions between loci of one-carbon metabolism modulate susceptibility to breast cancer.  

PubMed

In view of growing body of evidence substantiating the role of aberrations in one-carbon metabolism in the pathophysiology of breast cancer and lack of studies on gene-gene interactions, we investigated the role of dietary micronutrients and eight functional polymorphisms of one-carbon metabolism in modulating the breast cancer risk in 244 case-control pairs of Indian women and explored possible gene-gene interactions using Multifactor dimensionality reduction analysis (MDR). Dietary micronutrient status was assessed using the validated Food Frequency Questionnaire. Genotyping was done for glutamate carboxypeptidase II (GCPII) C1561T, reduced folate carrier (RFC)1 G80A, cytosolic serine hydroxymethyltransferase (cSHMT) C1420T, thymidylate synthase (TYMS) 5'-UTR tandem repeat, TYMS 3'-UTR ins6/del6, methylenetetrahydrofolate reductase (MTHFR) C677T, methyltetrahydrofolate-homocysteine methyltransferase (MTR) A2756G, methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) A66G polymorphisms by using the PCR-RFLP/AFLP methods. Low dietary folate intake (P < 0.001), RFC1 G80A (OR: 1.38, 95% CI 1.06-1.81) and MTHFR C677T (OR: 1.74 (1.11-2.73) were independently associated with the breast cancer risk whereas cSHMT C1420T conferred protection (OR: 0.72, 95% CI 0.55-0.94). MDR analysis demonstrated a significant tri-variate interaction among RFC1 80, MTHFR 677 and TYMS 5'-UTR loci (P (trend) < 0.02) with high-risk genotype combination showing inflated risk for breast cancer (OR 4.65, 95% CI 1.77-12.24). To conclude, dietary as well as genetic factors were found to influence susceptibility to breast cancer. Further, the current study highlighted the importance of multi-loci analyses over the single-locus analysis towards establishing the epistatic interactions between loci of one-carbon metabolism modulate susceptibility to the breast cancer. PMID:21161404

Naushad, Shaik Mohammad; Pavani, Addepalli; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Kutala, Vijay Kumar

2010-12-14

287

Modulatory effect of plasma folate and polymorphisms in one-carbon metabolism on catecholamine methyltransferase (COMT) H108L associated oxidative DNA damage and breast cancer risk.  

PubMed

The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2'-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5'-UTR 3R2R, TYMS 3'-UTR ins6/de16. Increased plasma 8-oxodG were observed in cases compared to controls (mean +/- SE: 5.59 +/- 0.60 vs. 3.50 +/- 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk. PMID:22053698

Naushad, Shaik Mohammad; Pavani, Addepalli; Rupasree, Yedluri; Sripurna, Deepti; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadha Rao; Kutala, Vijay Kumar

2011-08-01

288

Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast.  

PubMed

In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2'deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR-RFLP and PCR-AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08, P < 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (P = 0.034) and methionine synthase reductase (MTRR) A66G (P = 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (P < 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml, P < 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (P < 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer. PMID:21987236

Naushad, Shaik Mohammad; Prayaga, Aruna; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Kutala, Vijay Kumar

2011-10-11

289

Association of aberrations in one-carbon metabolism with molecular phenotype and grade of breast cancer.  

PubMed

We have earlier demonstrated the role of aberrant one-carbon metabolism in the etiology of breast cancer. In the current study, we examine the clinical utility of these factors in predicting the subtype of breast cancer and as indicators of disease progression. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-amplified fragment length polymorphism (AFLP) approaches were used for genetic analysis. Plasma folate and homocysteine were measured using Axsym folate kit and reverse phase HPLC, respectively. Multiple linear regression models were used to test the predictability of disease progression. Luminal A subtype was associated with late age of onset, higher body mass index and lack of family history of breast cancer. Thymidylate synthase (TYMS) 5'-UTR 28 bp tandem repeat (OR: 2.09, 95% CI: 1.05-4.16) and methylene tetrahydrofolate reductase (MTHFR) C677T (OR: 4.10, 95% CI: 1.40-11.95) were strongly associated with Luminal B. Reduced folate carrier (RFC1) G80A (OR: 2.92, 95% CI: 1.22-6.97) and methionine synthase (MTR) A2756G (OR: 4.71, 95% CI: 1.66-13.31) polymorphisms were associated with LuminA-HH subtype while MTHFR C677T showed association with HER-enriched (OR: 30.41, 95% CI: 6.47-142.91). Cytosolic serine hydroxymethyltransferase (cSHMT) conferred protection against basal-like breast cancer (OR: 0.47, 95% CI: 0.22-0.98). HER-enriched and basal-like subtypes showed positive association with familial breast cancer and inverse association with plasma folate. Hyperhomocysteinemia was observed in Luminal B and basal-like subtypes. Multiple linear regression models of aberrant one-carbon metabolism were found to be moderate predictors of breast cancer grade (area under the receiver operating characteristic curve, C = 0.72, 95% CI: 0.58-0.87, P = 0.008). To conclude, aberrations in one-carbon metabolism predict the subtype of breast cancer and disease progression. PMID:22086855

Naushad, Shaik Mohammad; Pavani, Addepalli; Rupasree, Yedluri; Divyya, Shree; Deepti, Sripurna; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Prayaga, Aruna; Kutala, Vijay Kumar

2011-11-15

290

Neutronic analysis of the conversion of HEU to LEU fuel for a 5-MW MTR core  

SciTech Connect

In recent years, due to cessation of highly enriched uranium (HEU) fuel supply, practical steps have been taken to substitute HEU fuel in almost all research reactors by medium-enriched uranium or low-enriched uranium (LEU) fuels. In this study, a neutronic calculation of a 5-MW research reactor core fueled with HEU (93% /sup 235/U) is presented. In order to assess the performance of the core with the LEU (< 20%) fuel replacement, while keeping fuel element geometry nearly unchanged, several different /sup 235/U loadings were examined. The core consists of 22 standard fuel elements (SFEs) and 6 control fuel elements (CFEs). Each fuel elements has 18 curved plates of which two end plates are dummies. Initial /sup 235/U content is 195 g /sup 235/U/SFE and 9.7 g /sup 235/U/CFE or /PFE. In all calculations the permitted changes to the fuel elements are (a) 18 active plates per SFE, (b) fuel plates assumed to be flat, and (c) 8 or 9 active plates per CFE.

Pazirandeh, A.; Bartsch, G.

1987-01-01

291

Simplified numerical model for defining Ledinegg flow instability margins in MTR research reactor  

Microsoft Academic Search

Establishment of safety margins and the corresponding operating condition limits will ensure achievement of a safe operation of nuclear installations. For this purpose, several critical phenomena have been analyzed theoretically and experimentally and a great number of models and correlations are made available. Among these critical issues the well-known flow instability has been intensively investigated by several authors especially for

Tewfik Hamidouche; Nouara Rassoul; El-Khider Si-Ahmed; Hakim El Hadjen; Anis Bousbia-salah

2009-01-01

292

DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity  

Microsoft Academic Search

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and\\/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to

M. Kubicki; C. F. Westin; P. G. Nestor; R. V. Mulkern; S. E. Maier; M. Niznikiewicz; E. E. Connor; J. J. Levitt; M. Frumin; R. Kikinis; F. A. Jolesz; R. W. McCarley; M. E. Shenton

2005-01-01

293

Immobilisation of MTR Waste in Cement (Product Evaluation). Annual Report March 1985.  

National Technical Information Service (NTIS)

This report describes work performed at Winfrith under the UKAEA's research and development programme on radioactive waste management. The work carried out during April 1984 to March 1985 on the evaluation of laboratory and 200 dm sup 3 scale products of ...

C. G. Howard D. L. G. Smith J. R. A. Williams

1986-01-01

294

46 CFR 11.950 - Subjects for engineer endorsements.  

Code of Federal Regulations, 2010 CFR

...Table 11.950âSubjects for Engineer Endorsements Unlimited chief engineer STM MTR Unlimited 1st asst. engineer STM MTR Unlimited 2nd asst. engineer STM MTR Unlimited 3rd asst. engineer STM MTR Chief engineer limited...

2009-10-01

295

46 CFR 11.950 - Subjects for engineer endorsements.  

Code of Federal Regulations, 2010 CFR

...Table 11.950âSubjects for Engineer Endorsements Unlimited chief engineer STM MTR Unlimited 1st asst. engineer STM MTR Unlimited 2nd asst. engineer STM MTR Unlimited 3rd asst. engineer STM MTR Chief engineer limited...

2010-10-01

296

Prediction, analysis and solution of the flow inversion phenomenon in a typical MTR-reactor with upward core cooling  

Microsoft Academic Search

Research reactors of power greater than 20MW are usually designed to be cooled with upward coolant flow direction inside the reactor core. This is mainly to prevent flow inversion problems following a pump coast down. However, in some designs and under certain operating conditions, flow inversion phenomenon is predicted. In the present work, the best-estimate Material Testing Reactors Thermal-Hydraulic Analysis

Salah El-Din El-Morshedy

2011-01-01

297

Program Guide for Basic Precision Machining 8754000 (IN48.052300) and Precision Machining MTR0470 (IN48.050300).  

ERIC Educational Resources Information Center

|This competency-based program guide provides course content information and procedures for secondary schools, postsecondary vocational schools, and community colleges in Florida that conduct programs in basic precision machining and precision machining. The first section is on legal authority, which applies to all vocational education programs in…

University of South Florida, Tampa. Dept. of Adult and Vocational Education.

298

Evidence for the Assembly of a Bacterial Tripartite Multidrug Pump with a Stoichiometry of 3:6:3*  

PubMed Central

The multiple transferable resistance (mTR) pump from Neisseria gonorrhoeae MtrCDE multidrug pump is assembled from the inner and outer membrane proteins MtrD and MtrE and the periplasmic membrane fusion protein MtrC. Previously we established that while there is a weak interaction of MtrD and MtrE, MtrC binds with relatively high affinity to both MtrD and MtrE. MtrD conferred antibiotic resistance only when it was expressed with MtrE and MtrC, suggesting that these proteins form a functional tripartite complex in which MtrC bridges MtrD and MtrE. Furthermore, we demonstrated that MtrC interacts with an intraprotomer groove on the surface of MtrE, inducing channel opening. However, a second groove is apparent at the interface of the MtrE subunits, which might also be capable of engaging MtrC. We have now established that MtrC can be cross-linked to cysteines placed in this interprotomer groove and that mutation of residues in the groove impair the ability of the pump to confer antibiotic resistance by locking MtrE in the closed channel conformation. Moreover, MtrE K390C forms an intermolecular disulfide bond with MtrC E149C locking MtrE in the open channel conformation, suggesting that a functional salt bridge forms between these residues during the transition from closed to open channel conformations. MtrC forms dimers that assemble into hexamers, and electron microscopy studies of single particles revealed that these hexamers are arranged into ring-like structures with an internal aperture sufficiently large to accommodate the MtrE trimer. Cross-linking of single cysteine mutants of MtrC to stabilize the dimer interface in the presence of MtrE, trapped an MtrC-MtrE complex with a molecular mass consistent with a stoichiometry of 3:6 (MtrE3MtrC6), suggesting that dimers of MtrC interact with MtrE, presumably by binding to the two grooves. As both MtrE and MtrD are trimeric, our studies suggest that the functional pump is assembled with a stoichiometry of 3:6:3.

Janganan, Thamarai K.; Bavro, Vassiliy N.; Zhang, Li; Matak-Vinkovic, Dijana; Barrera, Nelson P.; Venien-Bryan, Catherine; Robinson, Carol V.; Borges-Walmsley, Maria Ines; Walmsley, Adrian R.

2011-01-01

299

Evidence for the assembly of a bacterial tripartite multidrug pump with a stoichiometry of 3:6:3.  

PubMed

The multiple transferable resistance (mTR) pump from Neisseria gonorrhoeae MtrCDE multidrug pump is assembled from the inner and outer membrane proteins MtrD and MtrE and the periplasmic membrane fusion protein MtrC. Previously we established that while there is a weak interaction of MtrD and MtrE, MtrC binds with relatively high affinity to both MtrD and MtrE. MtrD conferred antibiotic resistance only when it was expressed with MtrE and MtrC, suggesting that these proteins form a functional tripartite complex in which MtrC bridges MtrD and MtrE. Furthermore, we demonstrated that MtrC interacts with an intraprotomer groove on the surface of MtrE, inducing channel opening. However, a second groove is apparent at the interface of the MtrE subunits, which might also be capable of engaging MtrC. We have now established that MtrC can be cross-linked to cysteines placed in this interprotomer groove and that mutation of residues in the groove impair the ability of the pump to confer antibiotic resistance by locking MtrE in the closed channel conformation. Moreover, MtrE K390C forms an intermolecular disulfide bond with MtrC E149C locking MtrE in the open channel conformation, suggesting that a functional salt bridge forms between these residues during the transition from closed to open channel conformations. MtrC forms dimers that assemble into hexamers, and electron microscopy studies of single particles revealed that these hexamers are arranged into ring-like structures with an internal aperture sufficiently large to accommodate the MtrE trimer. Cross-linking of single cysteine mutants of MtrC to stabilize the dimer interface in the presence of MtrE, trapped an MtrC-MtrE complex with a molecular mass consistent with a stoichiometry of 3:6 (MtrE(3)MtrC(6)), suggesting that dimers of MtrC interact with MtrE, presumably by binding to the two grooves. As both MtrE and MtrD are trimeric, our studies suggest that the functional pump is assembled with a stoichiometry of 3:6:3. PMID:21610073

Janganan, Thamarai K; Bavro, Vassiliy N; Zhang, Li; Matak-Vinkovic, Dijana; Barrera, Nelson P; Venien-Bryan, Catherine; Robinson, Carol V; Borges-Walmsley, Maria Inês; Walmsley, Adrian R

2011-05-24

300

Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases.  

PubMed

Venous thrombosis is a significant cause of morbidity and mortality in patients with malignancies. We aimed to investigate the association between prothrombotic gene polymorphisms detected in lung cancer cases and deep venous thrombosis (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which 33 developed DVT, were enrolled. Multiplex PCR technique and reverse hybridization strip assay were performed on DNA extracted from peripheral blood, in order to analyze prothrombin G20210A, factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17% homozygous). The presence of homozygous MTHFR A1298C mutation was significantly associated with DVT (P=0.020). Comparing the lung cancer patients with and without DVT, only MTHFR A1298C gene polymorphism differed significantly (P=0.040). We determined a higher rate of prothrombotic gene mutations in lung cancer patients who developed DVT. However, statistical significance was achieved only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for disturbance of hemostatic metabolism should also be considered in lung cancer patients. PMID:21080081

Arslan, Sulhattin; Manduz, Sinasi; Epöztürk, Kür?at; Karahan, O?uz; Akkurt, Ibrahim

2010-11-16

301

I polimorfismi della metilentetraidrofolatoreduttasi (MTHFR) nel trattamento con methotrexate di pazienti con artrite reumatoide. Revisione della letteratura ed esperienza personale* Methylenetetrahydrofolate reductase polymorphisms in methotrexate treatment of rheumatoid arthritis patients. Review of the literature and personal experience  

Microsoft Academic Search

SUMMARY Methotrexate is still a mainstay of rheumatoid arthritis treatment, but a significant variability in drug response is ob- served among patients. It has been proposed that C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the folate pathway, could be related to its efficacy and toxicity. Many stud- ies have investigated the predictive value of such

M. Taraborelli; L. Andreoli; S. Archetti; M. Ferrari; R. Cattaneo; A. Tincani

302

Functional inference of methylenetetrahydrofolate reductase gene polymorphisms on enzyme stability as a potential risk factor for Down syndrome in Croatia.  

PubMed

Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two common MTHFR polymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence of MTHFR C677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n=102) or DS pregnancy (n=9) and mothers with a healthy child (n=141). MTHFR C677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using chi square test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of the MTHFR C677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility that MTHFR polymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population. PMID:20592453

Vranekovi?, Jadranka; Babi? Bozovi?, Ivana; Starcevi? Cizmarevi?, Nada; Bureti?-Tomljanovi?, Alena; Risti?, Smiljana; Petrovi?, Oleg; Kapovi?, Miljenko; Brajenovi?-Mili?, Bojana

2010-01-01

303

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies  

PubMed Central

Background 5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk. Methods Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity. Results C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE?=?0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P?=?0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE?=?1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism. Conclusions The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.

2012-01-01

304

HWMA/RCRA Closure Plan for the TRA/MTR Warm Waste System Voluntary Consent Order SITE-TANK-005 Tank System TRA-007  

SciTech Connect

This Hazardous Waste Management Act/Resource Conservation and Recovery Act Closure Plan was developed for portions of the Test Reactor Area/Materials Test Reactor Warm Waste System located in the Materials Test Reactor Building (TRA-603) at the Reactor Technology Complex, Idaho National Laboratory Site, to meet a further milestone established under Voluntary Consent Order Action Plan SITE-TANK-005 for the Tank System TRA-007. The reactor drain tank and canal sump to be closed are included in the Test Reactor Area/Materials Test Reactor Warm Waste System. The reactor drain tank and the canal sump will be closed in accordance with the interim status requirements of the Hazardous Waste Management Act/Resource Conservation and Recovery Act as implemented by the Idaho Administrative Procedures Act 58.01.05.009 and Code of Federal Regulations 265. This closure plan presents the closure performance standards and methods for achieving those standards.

K. Winterholler

2007-01-30

305

Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae.  

National Technical Information Service (NTIS)

The MtrC-MtrD-MtrE multidrug efflux pump of Neisseria gonorrhoeae confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the mtrCDE ope...

D. Golparian E. A. Ohneck P. J. Johnson V. Dhulipala Y. M. Zalucki

2011-01-01

306

MTHFR gene polymorphisms in bladder cancer in the Turkish population.  

PubMed

Bladder cancer is the 9th most common cancer and is responsible for malignancy related death all on the world. Folate and folate related enzyme polymorphisms related to the cancer risk. The methylene tethrahydrofolate reductase (MTHFR) enzyme is folate related and association of bladder cancer and MTHFR gene. Our purpose was to assess the prevalence of MTHFR gene 677 CT and 1298 AC polymorphisms and Bladder cancer in Turkey. We intended that bladder cancer patients and controls and we used the Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. The MTHFR gene C677T and A1298C polymorphisms were associated with an increased risk of bladder cancer in our population (For the MTHFR gene C677T polymorphism and A1298C polymorphism; p=0.036<0.05; p=0.278>0.05 respectively). Consequently, the MTHFR gene C677T polymorphism augments the risk of bladder cancer in Turkey. PMID:22126575

Izmirli, Muzeyyen; Inandiklioglu, Nihal; Abat, Deniz; Alptekin, Davut; Demirhan, Osman; Tansug, Zuhtu; Bayazit, Yildirim

2011-01-01

307

Case-control Study of methylenetetrahydrofolate reductase mutations and hyperhomocysteinemia and risk of stroke.  

PubMed

The association of factor V-Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations with stroke was investigated in 118 patients with stroke and 120 control subjects. MTHFR 677TT (P < .001) and 1298CC (P < .001), but not factor V-Leiden (P = .179), genotypes were associated with stroke. The C677T but not A1298C MTHFR mutation was associated with elevated homocysteine levels in patients and control subjects. In addition to hypertension, the significant predictors for stroke were MTHFR 677CT and TT and A1298CC genotypes, together with hyperhomocysteinemia, indicating a synergistic effect of MTHFR mutations with elevated homocysteine and other risk factors in pathogenesis of stroke. PMID:19717029

Almawi, Wassim Y; Khan, Abdulmajeed; Al-Othman, Sara S; Bakhiet, Moiz

308

Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder  

PubMed Central

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.

Gokcen, Cem; Kocak, Nadir; Pekgor, Ahmet

2011-01-01

309

5,10-Methylenetetrahydrofolate Reductase Gene Variants and Congenital Anomalies: A HuGE Review  

Microsoft Academic Search

The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism. The MTHFR gene is located on chromosome 1 (1p36.3), and two common alleles, the C677T (thermolabile) allele and the A1298C allele, have been described. The population frequency of C677T homozygosity ranges from 1% or less among Blacks from Africa and the United States to 20% or more among Italians and

Lorenzo D. Botto; Quanhe Yang

2000-01-01

310

Genetic Polymorphisms in Venous Thrombosis and Pulmonary Embolism After Total Hip Arthroplasty: A Pilot Study  

Microsoft Academic Search

Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined\\u000a presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary\\u000a embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate\\u000a reductase (MTHFR) C677T and A1298C, and plasminogen activator

Juergen Ringwald; Annika Berger; Werner Adler; Cornelia Kraus; Rocco P. Pitto

2009-01-01

311

Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores)  

Microsoft Academic Search

SUMMARY: BACKGROUND: The Azorean population presents the highest standardized mortality rate for cardiovascular diseases (CVD) when compared to mainland Portugal and other populations. Since thrombosis is a common cause of CVD, we assessed four polymorphisms in three thrombotic risk genes – F5 (G1691A), F2 (G20210A) and MTHFR (C677T, A1298C), in 469 healthy blood donors from São Miguel Island (Azores). We

Claudia C Branco; Tânia Pereirinha; Rita Cabral; Paula R Pacheco; Luisa Mota-Vieira

2009-01-01

312

Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population  

Microsoft Academic Search

Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on\\u000a the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggested that a defective methionine\\u000a synthase (MS) enzyme could be a critical defect in folate-related

Patrizia De Marco; Maria Grazia Calevo; Anna Moroni; Lorenza Arata; Elisa Merello; Richard H. Finnell; Huiping Zhu; Luciano Andreussi; Armando Cama; Valeria Capra

2002-01-01

313

Association of MTHFR gene polymorphisms with breast cancer survival  

Microsoft Academic Search

BACKGROUND: Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. METHODS: African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer

Damali N Martin; Brenda J Boersma; Tiffany M Howe; Julie E Goodman; Leah E Mechanic; Stephen J Chanock; Stefan Ambs

2006-01-01

314

MTHFR polymorphisms’ influence on outcome and toxicity in acute lymphoblastic leukemia patients  

Microsoft Academic Search

Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients.Relapse free survival and event free survival between homozygous

Patrizia Chiusolo; Giovanni Reddiconto; Giuliana Farina; Alice Mannocci; Alessia Fiorini; Mariangela Palladino; Giuseppe La Torre; Luana Fianchi; Federica Sorà; Luca Laurenti; Giuseppe Leone; Simona Sica

2007-01-01

315

The association between methylene-tetrahydrofolate reductase gene polymorphism and lung cancer risk  

Microsoft Academic Search

This study aimed to determine the relation between methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism and lung\\u000a cancer risk and the frequency of this polymorphism. The study involved 64 lung cancer patients (the study group) with definitive\\u000a diagnosis and 61 noncancerous subjects (the control group). MTHFR C677T and A1298C mutation analysis was made using DNA isolated\\u000a from peripheric blood and multiplex PCR

Sulhattin Arslan; Sule Karadayi; Malik Ejder Yildirim; Ozturk Ozdemir; Ibrahim Akkurt

2011-01-01

316

Methylenetetrahydrofolate Reductase (MTHFR) from Mediterranean to Sub-Saharan Areas  

Microsoft Academic Search

There are differences in the allele frequency of MTHFR polymorphism between Western and African population. The aim of this study is to determinate the prevalence of MTHFR C677T and A1298C polymorphisms in young and old people living in different areas from Mediterranean to sub- Saharan areas. The observed vs expected genotype frequencies of 677T were in Hardy Weinberg equilibrium, with

Rosa Chillemi; Andrea Angius; Ivana Persico; Alessandro Sassu; Dionigio A. Prodi; Salvatore Musumeci

2006-01-01

317

Role of Thrombotic Risk Factors in End-Stage Renal Disease  

Microsoft Academic Search

Introduction: Genetic polymorphisms that are found among factors of the coagulation cascade are factor V leiden mutation (FVL), prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR), reported for thrombotic complications. We have investigated the associations of these gene polymorphisms in patients with end-stage renal disease (ESRD). Methods: We genotyped 258 patients for FV G1691A, PT G20210A, and MTHFR (C677T, A1298C) gene by

Gaurav Tripathi; Satya Narayan Sankhwar; Raj Kumar Sharma; Vinod Pandirikkal Baburaj; Suraksha Agrawal

2010-01-01

318

Mutations and Polymorphisms in Genes Affecting Hemostasis Proteins and Homocysteine Metabolism in Children with Arterial Ischemic Stroke  

Microsoft Academic Search

Background: The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors. Aim: To compare the distributions of mutations\\/polymorphisms in genes affecting hemostasis (factor V Leiden – FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103

A. Komitopoulou; H. Platokouki; Z. Kapsimali; H. Pergantou; E. Adamtziki; S. Aronis

2006-01-01

319

Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation  

Microsoft Academic Search

To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a

Inho Kim; Kyung-Hun Lee; Jin Hee Kim; Eun Kyung Ra; Sung-Soo Yoon; Yun-Chul Hong; Sung Sup Park; Chul Soo Kim; Byoung Kook Kim

2007-01-01

320

Methylenetetrahydrofolate reductase genotype association with the risk of follicular lymphoma.  

PubMed

The metabolism of folate is essential in DNA synthesis, and polymorphisms of genes involved in such metabolism have been implicated in many types of cancer. Among these, the methylene tetrahydrofolate reductase gene (MTHFR) encodes an enzyme that converts folate to a methyl donor used for DNA methylation. We studied the association between the different genotypes of the two most common MTHFR polymorphisms, C677T and A1298C, and the risk of follicular lymphoma (FL). For this purpose, 55 previously diagnosed FL patients and 170 normal control subjects were examined using polymerase chain reaction followed by restriction fragment length polymorphism. The frequency of the A1298C CC homozygous mutant genotype was significantly higher in patients with FL than in control subjects (OR = 3.51, 95% CI = 1.39-8.86, P = 0.008). No such association was found for the heterozygous A1298C AC genotype (OR = 1.08, 95% CI = 0.55-2.12, P = 0.83). On the other hand, no significant association was found for either the C677T CT heterozygous genotype (OR = 0.79, 95% CI = 0.42-1.51, P = 0.49) or the C677T TT homozygous mutant genotype (OR = 0.55, 95% CI = 0.12-2.65, P = 0.46). The present findings add to the very few reports suggesting a link between the A1298C CC homozygous MTHFR genotype and a higher risk of developing FL, and the first such in a Jordanian population. PMID:19963111

Ismail, Said I; Ababneh, Nida A; Khader, Yousef; Abu-Khader, Ahmad A; Awidi, Abdullah

2009-12-01

321

Prevalence of methylene tetrahydrofolate reductase polymorphism in South Indian population  

Microsoft Academic Search

Prevalence of methylene tetrahydrofolate reductase (MTHFR) gene mutations in South Indian population was investigated from a total of 608 samples, 420 adults and 188 newborns. Detection of mutation was carried out focussing on the two most common mutations of the MTHFR gene (C677T and A1298C) using PCR- based RFLP method. T-allele frequency was almost simi- lar between the newborns and

A. Radha; Rama Devi; V. Govindaiah; G. Ramakrishna; S. M. Naushad

322

MTHFR 677 CT\\/MTHFR 1298 CC genotypes are associated with increased risk of hypertension in Indians  

Microsoft Academic Search

The goals of our present study were to measure plasma homocysteine levels and determine their association with methylenetetrahydrofolate\\u000a reductase (MTHFR) gene polymorphisms (C677T and A1298C) in essential hypertensive subjects. Plasma total homocysteine and\\u000a folic acid levels were measured in essential hypertensive patients (n = 153) before and after oral supplementation with either 5 mg folic acid tablet\\/day or 5 mg placebo\\/day for 4 weeks and

Suchita Markan; Meenakshi Sachdeva; Badan Singh Sehrawat; Savita Kumari; Sanjay Jain; Madhu Khullar

2007-01-01

323

A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia  

Microsoft Academic Search

A meta-analysis of case–control studies that investigated the association between the C677T and\\/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds ratios (OR) of various genetic contrasts of each polymorphism were estimated using random (RE) and fixed effects (FE) models. Pooled ORs for combined genotypes and haplotypes were estimated after

Elias Zintzaras; Theocharis Koufakis; Panayiotis D. Ziakas; Paraskevi Rodopoulou; Stavroula Giannouli; Michael Voulgarelis

2006-01-01

324

Metabolic and Genetic Risk Factors for Migraine in Children  

Microsoft Academic Search

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C

F Bottini; ME Celle; MG Calevo; S Amato; G Minniti; L Montaldi; D Di Pasquale; R Cerone; E Veneselli; AC Molinari

2006-01-01

325

Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis  

Microsoft Academic Search

To clarify the influence of MTHFR C677T and A1298C polymorphisms on gastric cancer (GC), a meta-analysis of eight case-control studies (1,584\\/2,785 cases\\/controls) was carried out. Overall, there was moderate heterogeneity among studies, and the C677T allele T was associated with a 27% increased risk of GC compared with C allele: the random effects (RE) OR (95% confidence interval in parenthesis)

Elias Zintzaras

2006-01-01

326

MTHFR (677 and 1298) and IL6-174 G\\/C genes in pathogenesis of Alzheimer's and vascular dementia and their epistatic interaction  

Microsoft Academic Search

Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G\\/C

Nasim Mansoori; Manjari Tripathi; Kalpana Luthra; Rizwan Alam; Ramakrishnan Lakshmy; Subhadra Sharma; Subramanyam Arulselvi; Shama Parveen; Asok K. Mukhopadhyay

327

Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease.  

PubMed

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD. PMID:23484733

Huang, Yang; Teranishi, Masaaki; Uchida, Yasue; Nishio, Naoki; Kato, Ken; Otake, Hironao; Yoshida, Tadao; Sone, Michihiko; Sugiura, Saiko; Ando, Fujiko; Shimokata, Hiroshi; Nakashima, Tsutomu

2013-03-13

328

Methylenetetrahydrofolate reductase polymorphism C677T is a protective factor for pediatric acute lymphoblastic leukemia in the Chinese population: a meta-analysis.  

PubMed

Two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, were hypothesized to decrease the risk of acute lymphoblastic leukemia (ALL). Studies examining the associations between these two polymorphisms and ALL susceptibility drew inconsistent results. To obtain a reliable conclusion in a Chinese population, we carried out a meta-analysis. In total, 11 studies on C677T polymorphism (1597 cases and 2295 controls) and 10 studies on A1298C polymorphism (1553 cases and 2224 controls) were included in the meta-analysis. We found a significant association between the 677T variant and reduced ALL risk in Chinese children (Dominant model: odds ratio [OR(FE)]=0.73, 95% confidence interval [CI]: 0.63-0.86, p<0.01). Heterogeneity between the studies in the children subgroup was weak and vanished after excluding one study deviating from HWE in the control group (p>0.1). In the adult subgroup, there was no significant association between the C677T variant and ALL risk (Dominant model: OR(RE)=0.88, 95% CI: 0.45-1.72, p=0.72). Significant heterogeneity was found in the adult subgroup in all the genetic model tests (p<0.1). The A1298C polymorphism had an effect on ALL risk neither in adults (Dominant model: OR(FE)=0.95, 95% CI: 0.71-1.27, p=0.72) nor in children (Dominant model: OR(FE)=1.02, 95% CI: 0.87-1.21, p=0.77). No significant heterogeneity between studies on A1298C polymorphism was found in the meta-analysis (p>0.1). The results showed that there was a protective effect of the MTHFR C677T variant on ALL risk in Chinese children. PMID:23061880

Wang, Haigang; Meng, Lujing; Zhao, Lixia; Wang, Jiali; Liu, Xinchun; Mi, Wenjie

2012-10-12

329

Analysis of MTHFR polymorphisms and P16 methylation and their correlation with clinical–biological features of multiple myeloma  

Microsoft Academic Search

Background  Low folate intake and changes in folate metabolism due to polymorphisms in the methylentetrahydrofolate reductase (MTHFR) gene have been associated with myelomagenesis. However, controversial data have been published regarding a protective role of variant alleles of MTHFR on MM.Patients and methods  To investigate the influence of two common polymorphisms of MTHFR C677T and A1298C on the risk of multiple myeloma (MM),

Patrizia Chiusolo; Giuliana Farina; Rossana Putzulu; Giovanni Reddiconto; Alessia Fiorini; Valerio De Stefano; Elena Rossi; Mariangela Palladino; Giuseppe Leone; Simona Sica

2006-01-01

330

Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls  

Microsoft Academic Search

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely\\u000a reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast\\u000a cancer, an updated meta-analysis of all available studies relating C677T and\\/or A1298C polymorphisms of MTHFR gene to the\\u000a risk of breast cancer was conducted. Eligible articles

Xiaowei Qi; Xiangyu Ma; Xinhua Yang; Linjun Fan; Yi Zhang; Fan Zhang; Li Chen; Yan Zhou; Jun Jiang

2010-01-01

331

Genetic polymorphisms of methylenetetrahydrofolate reductase and promoter methylation of MGMT and FHIT genes in diffuse large B cell lymphoma risk in Middle East  

Microsoft Academic Search

Diffuse large B cell lymphoma (DLBCL) is one of the most common non-Hodgkin’s lymphoma types. Methylenetetrahydrofolate reductase\\u000a (MTHFR) balances the pool of folate coenzymes in one carbon metabolism of deoxyribonucleic acid (DNA) synthesis and methylation;\\u000a both are implicated in carcinogenesis of many types of cancer including lymphoma. Two common variants in the MTHFR gene (C677T\\u000a and A1298C) have been associated

Abdul K. Siraj; Muna Ibrahim; Maha Al-Rasheed; Rong Bu; Prashant Bavi; Zeenath Jehan; Jehad Abubaker; Walid Murad; Fouad Al-Dayel; Adnan Ezzat; Hassan El-Solh; Shahab Uddin; Khawla Al-Kuraya

2007-01-01

332

MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women  

Microsoft Academic Search

To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk, we conducted a case–control study with 669 cases and 682 population-based controls in the Jiangsu Province of China. MTHFR C677T and A1298C genotypes were identified using PCR–RFLP (restrictrion fragment length polymorphism) methods. Dietary folate intake was assessed using an

Chang-Ming Gao; Jin-Hai Tang; Hai-Xia Cao; Jian-Hua Ding; Jian-Zhong Wu; Jie Wang; Yan-Ting Liu; Su-Ping Li; Ping Su; Keitaro Matsuo; Toshiro Takezaki; Kazuo Tajima

2009-01-01

333

Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups  

Microsoft Academic Search

Objective To determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in women of different ethnic groups and to relate these common mutations to plasma homocysteine, red cell folate, and serum folate. Design A one-time fasting blood sample was obtained for MTHFR genotype (C677T and A1298C) determinations (n=433). Serum folate, red cell folate, and homocysteine analyses were performed in nonfolic

Setareh Torabian Esfahani; Edward A Cogger; Marie A Caudill

2003-01-01

334

MTHFR Polymorphisms Involved in Vitamin B 12 Deficiency Associated with Atrophic Gastritis  

Microsoft Academic Search

Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological\\u000a dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic\\u000a DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect\\u000a to hematological parameters, B12 and folate levels, and neurological symptoms. The two MTHFR polymorphisms

Mariangela Palladino; Patrizia Chiusolo; Giovanni Reddiconto; Sara Marietti; Daniela De Ritis; Giuseppe Leone; Simona Sica

2009-01-01

335

Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk  

Microsoft Academic Search

Functional polymorphisms in genes encoding enzymes involved in folate metabolism might modulate head and neck carcinoma risk\\u000a because folate participates in DNA methylation and synthesis. We therefore conducted a case–control study of 853 individuals\\u000a (322 head and neck cancer cases and 531 non-cancer controls) to investigate associations among MTHFR C677T and MTHFR A1298C polymorphisms and head and neck squamous cell

Ana Lívia Silva Galbiatti; Mariangela Torreglosa Ruiz; Juliana Olsen Rodrigues; Luiz Sérgio Raposo; José Victor Maníglia; Érika Cristina Pavarino; Eny Maria Goloni-Bertollo

336

Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population  

Microsoft Academic Search

Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH)\\u000a in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed\\u000a factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and\\u000a A1298C polymorphisms in 71 patients (53 men, 18

Jun-Dong Chang; Mina Hur; Sang-Soo Lee; Je-Hyun Yoo; Kyu Man Lee

2008-01-01

337

Genotyping of two single nucleotide polymorphisms in 5,10-methylenetetrahydrofolate reductase by multiplex polymerase chain reaction and capillary electrophoresis  

Microsoft Academic Search

Two single nucleotide polymorphisms (SNPs) of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, A1298C and C677T, were widely considered to be related with various neoplasia disorders. We established a simple and effective capillary electrophoresis (CE) method for detection of two SNPs in MTHFR gene simultaneously. DNA samples were amplified by multiplex PCR with universal fluorescence-labeled primer and analyzed by single-strand conformation polymorphism (SSCP)-CE

Hui-Ling Cheng; Shyh-Shin Chiou; Yu-Mei Liao; Yen-Ling Chen; Shou-Mei Wu

2011-01-01

338

A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia.  

PubMed

Methotrexate (MTX) is an important component of therapy used to treat childhood acute lymphoblastic leukemia (ALL). Two single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect MTHFR activity. A large body of studies has investigated the potential role of MTHFR SNPs in MTX toxicity in pediatric ALL. However, the results are controversial. In this review and meta-analysis, we critically evaluate the relationship between the C677T and A1298C polymorphisms of MTHFR and MTX toxicity in pediatric ALL. The majority of published reports do not find associations between MTHFR polymorphisms and toxicity in pediatric ALL. When associations are reported, often the results are contradictory to each other. The meta-analysis confirms a lack of association. In conclusion, MTHFR, C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity in pediatric ALL.The Pharmacogenomics Journal advance online publication, 23 October 2012; doi:10.1038/tpj.2012.44. PMID:23089671

Lopez-Lopez, E; Martin-Guerrero, I; Ballesteros, J; Garcia-Orad, A

2012-10-23

339

The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in Cretan children with acute lymphoblastic leukemia.  

PubMed

Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Recently, many studies have examined factors influencing both the susceptibility to ALL and the metabolism of widely used chemotherapeutic agents. These factors include, among others, single-nucleotide polymorphisms in various genes, such as the gene encoding for methylenetetrahydrofolate reductase (MTHFR), which has been proven polymorphic at the nucleotide positions 677 and 1298. Thirty-five children with ALL and 48 healthy adults of Cretan origin were genotyped for the presence of the MTHFR 677 and 1298 single-nucleotide polymorphisms. The possible correlation of the polymorphisms with the risk for ALL and the presence of methotrexate-induced toxicities were examined. No significant association between the MTHFR genotypes and the susceptibility to ALL was observed. A borderline statistically significant relationship was detected after methotrexate administration, between the C677T genotype (polymorphisms) and leukopenia (p?=?0.050) and between the A1298C polymorphism and normal aspartate transaminase and alanine transaminase values (p?=?0.065 and p?=?0.053, respectively), which was strengthened for aspartate transaminase, after grouping the A1298A and A1298C genotypes together (p?=?0.039). In our population the MTHFR C677T and A1298C polymorphisms are related with hematologic toxicity and hepatotoxicity, respectively, and could be suggested as prognostic factors for these adverse events. PMID:21117954

Karathanasis, Nikolaos V; Stiakaki, Eftichia; Goulielmos, George N; Kalmanti, Maria

2010-11-30

340

Failure to confirm influence of Methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease  

PubMed Central

Background Huntington disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Recently, suggestive association has been reported between a single nucleotide polymorphism (SNP; rs1801131, also known as A1298C) in the methyltetrahydrofolate reductase (MTHFR) gene and AO of HD. 5,10-MTHFR is a key enzyme in the folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using part of a previously established study cohort plus additional patients and appropriate statistical methods, we reinvestigated two polymorphisms in the MTHFR gene, C677T and A1298C, as well as their association with AO in 167 HD patients. Results There was no statistically significant impact on AO for HD patients, neither of MTHFR SNPs nor of the combinations thereof. Conclusion Contrary to previously described evidence the A1298C polymorphism in the MTHFR gene does not appear to modulate AO of HD patients.

Hansen, Wiebke; Saft, Carsten; Andrich, Jurgen; Muller, Thomas; Wieczorek, Stefan; Epplen, Jorg T; Arning, Larissa

2005-01-01

341

Application of microarray-based method for methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the risk of gastric carcinoma in east China population.  

PubMed

The microarrays were fabricated to explore the relationship between methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T and A1298C) and risk of gastric carcinoma in Chinese population. The genomic DNA was isolated from 170 patients with gastric carcinoma and 140 age- and sex-matched control subjects. The frequencies of C677T genotype were: CC (47.9%), CT (40%), CT (12.1%) in control group and CC (35.9%), CT (45.9%), TT (18.2%) in gastric carcinoma group, respectively. The individuals with 677CT + TT or 677TT genotypes had a 1.67-fold (95% CI: 1.06-2.64) or 2.67-fold (95% CI: 1.382-5.341) increased risk of developing gastric carcinoma compared with those carrying 677CC genotype. The genotype of MTHFR gene A1298C allele was not significantly different between the two groups. We found that a joint effect exits between the MTHFR C677T and A1298C polymorphism on the risk of gastric carcinoma. Our results show that the single nucleotide polymorphisms in the MTHFR gene are associated with the risk of gastric carcinoma in the east China population. PMID:18019157

Li, Song; Ji, Meiju; He, Nongyue; Lu, Zuhong

2007-09-01

342

MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: A meta-analysis of 3511 cases and 2762 controls.  

PubMed

Published data regarding the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and prostate cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and prostate cancer risk. Six studies including 3511 cases and 2762 controls described C677T genotypes, among which four articles totalling 838 cases and 1121 controls described A1298C genotypes, were involved in this meta-analysis. Overall meta-analysis indicated that the 677T allele was more likely to exert a protective effect on prostate cancer risk (OR=0.81, 95% CI: 0.68-0.98) with a recessive genetic model. No association was found for the 677CT genotype and the 677TT mutant homozygote with prostate cancer risk compared with 677CC, with OR=1.13 (95% CI: 0.88-1.45) and OR=0.85 (95% CI: 0.71-1.03), respectively. No evidence of an association of MTHFR A1298C polymorphism with prostate cancer was found. This meta-analysis supports that the C677T of the MTHFR gene is a low-penetrance susceptibility gene for prostate cancer, and might provide protective effects against prostate cancer risk. PMID:19223177

Bai, Jian-Ling; Zheng, Ming-Hua; Xia, Xian; Ter-Minassian, Monica; Chen, Yong-Ping; Chen, Feng

2009-02-14

343

MTHFR polymorphisms and risk of chronic lymphocytic leukemia.  

PubMed

Folate availability is critical for DNA integrity, required for the transfer of methyl groups in the biosynthesis of thymidilate. Reduction of 5,10-methylenetetrahydrofolate, a donor for methylating dUMP to dTMP in DNA synthesis, to 5-methyltetrahydrofolate, the primary methyl donor for methionine synthesis, is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR). The MTHFR polymorphisms C677T and A1298C have been shown in some studies to alter the risk of a range of different malignancies. We evaluated the role of the C677T and A1298C polymorphisms on chronic lymphocytic leukemia (CLL) risk by genotyping 832 patients and 886 healthy controls. The odds ratio of CLL associated with 677CT and 677TT genotypes were 1.02 [95% confidence interval (95% CI), 0.83-1.24] and 0.90 (95% CI, 0.66-1.24), respectively. The odds ratio of CLL associated with 1298AC and 1298CC genotypes were 0.97 (95% CI, 0.79-1.18) and 0.88 (95% CI, 0.62-1.24), respectively. This data indicate that the MTHFR polymorphisms C677T and A1298C do not significantly contribute to an inherited genetic susceptibility to CLL. PMID:15598791

Rudd, Matthew F; Sellick, Gabrielle S; Allinson, Ruth; Matutes, Estella; Catovsky, Daniel; Houlston, Richard S

2004-12-01

344

Methylenetetrahydrofolate reductase gene polymorphisms in Turkish children with attention-deficit/hyperactivity disorder.  

PubMed

Attention-deficit/hyperactivity disorder (ADHD) is a common, multifactorial genetic disorder. The aim of the present study was to evaluate a possible association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and ADHD. There is evidence to suggest that MTHFR C677T and A1298C polymorphisms alter the function of the enzyme, causing reduced folate and increased homocysteine levels in plasma. Two polymorphisms of the MTHFR gene, C677T (rs1801133) and A1298C (rs1801131), were analyzed in a sample of 100 Diagnostic and Statistical Manual of Mental Disorders-IV-diagnosed ADHD and 300 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method. We did not find any association between MTHFR 677T allele, MTHFR 1298C allele, and ADHD. In addition, there was no genotype association between the MTHFR gene and ADHD (?(2)=1.711; df=2; p=0.425; ?(2)=2.946; df=2; p=0.229). Our data suggest that neither the MTHFR C677T polymorphism nor the MTHFR A1298C polymorphism was associated with ADHD in Turkish children. Thus, the MTHFR gene does not seem to play a role in the etiopathogenesis of ADHD in the cohort studied. PMID:21819229

Ergul, Emel; Sazci, Ali; Kara, Ihsan

2011-08-05

345

A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae  

PubMed Central

ABSTRACT The MtrC-MtrD-MtrE multidrug efflux pump of Neisseria gonorrhoeae confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the mtrCDE operon is differentially regulated by both a repressor, MtrR, and an activator, MtrA. The mtrR gene lies 250 bp upstream of and is transcribed divergently from the mtrCDE operon. Previous research has shown that mutations in the mtrR coding region and in the mtrR-mtrCDE intergenic region increase levels of gonococcal antibiotic resistance and in vivo fitness. Recently, a C-to-T transition mutation 120 bp upstream of the mtrC start codon, termed mtr120, was identified in strain MS11 and shown to be sufficient to confer high levels of antimicrobial resistance when introduced into strain FA19. Here we report that this mutation results in a consensus ?10 element and that its presence generates a novel promoter for mtrCDE transcription. This newly generated promoter was found to be stronger than the wild-type promoter and does not appear to be subject to MtrR repression or MtrA activation. Although rare, the mtr120 mutation was identified in an additional clinical isolate during sequence analysis of antibiotic-resistant strains cultured from patients with gonococcal infections. We propose that cis-acting mutations can develop in gonococci that significantly alter the regulation of the mtrCDE operon and result in increased resistance to antimicrobials.

Ohneck, Elizabeth A.; Zalucki, Yaramah M.; Johnson, Paul J. T.; Dhulipala, Vijaya; Golparian, Daniel; Unemo, Magnus; Jerse, Ann E.; Shafer, William M.

2011-01-01

346

Characterization of an electron conduit between bacteria and the extracellular environment  

PubMed Central

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ?-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment.

Hartshorne, Robert S.; Reardon, Catherine L.; Ross, Daniel; Nuester, Jochen; Clarke, Thomas A.; Gates, Andrew J.; Mills, Paul C.; Fredrickson, Jim K.; Zachara, John M.; Shi, Liang; Beliaev, Alex S.; Marshall, Matthew J.; Tien, Ming; Brantley, Susan; Butt, Julea N.; Richardson, David J.

2009-01-01

347

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

National Technical Information Service (NTIS)

The purpose is training in nutritional and molecular epidemiology to establish an independent investigator. The major hypothesis is that high folate intake is associated with a decreased breast cancer risk particularly among those with MTHFR, MTR, and MTR...

M. J. SHrubsole

2006-01-01

348

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

National Technical Information Service (NTIS)

The purpose is training in nutritional and molecular epidemiology to establish an independent investigator. The major hypothesis is that high folate intake is associated with a decreased breast cancer risk particularly among those with MTHFR, MTR, and MTR...

M. J. Shrubsole

2004-01-01

349

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

National Technical Information Service (NTIS)

The purpose is training in nutritional and molecular epidemiology to establish an independent investigator. The major hypothesis is that high folate intake is associated with a decreased breast cancer risk particularly among those with MTHFR, MTR, and MTR...

M. J. Shrubsole

2005-01-01

350

Pathophysiologic and electrophysiologic mechanisms of myofascial trigger points  

Microsoft Academic Search

Objective: To review recent clinical and basic science studies on myofascial trigger points (MTrPs) to facilitate a better understanding of the mechanism of an MTrP.Data Sources: English literature in the last 15 years regarding scientific investigations on MTrPs in either humans or animals.Study Selection: Research works, especially electrophysiologic studies, related to the pathophysiology of MTrP.Data Synthesis: (1) Studies on an

Chang-Zern Hong; David G. Simons

1998-01-01

351

Myofascial trigger points: pathophysiology and correlation with acupuncture points  

Microsoft Academic Search

SummaryA review is made of recent studies on myofascial trigger points (MTrP) and their mechanism is discussed. Clinical and basic science studies have shown that there are multiple MTrP loci in a MTrP region. A MTrP locus contains a sensory component (sensitive locus) and a motor component (active locus). A sensitive locus is a point from which tenderness or pain,

Chang-Zern Hong

2000-01-01

352

Treatment of myofascial pain syndrome  

Microsoft Academic Search

Myofascial pain syndrome (MPS) is caused by myofascial trigger points (MTrPs) located within taut bands of skeletal muscle\\u000a fibers. Treating the underlying etiologic lesion responsible for MTrP activation is the most important strategy in MPS therapy.\\u000a If the underlying pathology is not given the appropriate treatment, the MTrP cannot be completely and permanently inactivated.\\u000a Treatment of active MTrPs may be

Chang-Zern Hong

2006-01-01

353

Serial Magnetization Transfer Imaging in Acute Optic Neuritis  

ERIC Educational Resources Information Center

In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR

Hickman, S. J.; Toosy, A. T.; Jones, S. J.; Altmann, D. R.; Miszkiel, K. A.; MacManus, D. G.; Barker, G. J.; Plant, G. T.; Thompson, A. J.; Miller, D.H.

2004-01-01

354

Understanding effective treatments of myofascial trigger points  

Microsoft Academic Search

This article considers specific treatment approaches and the role of etiological mechanisms in terms of clinical feature characteristics of MTrPs: increased muscle tension, pain and tenderness, painful stretch range of motion, initiating causes of MTrPs. Final sections note additional treatments that are currently used, and summarize the etiological and clinical distinctions between MTrPs and fibromyalgia.

David G. Simons

2002-01-01

355

TRA Closure Plan REV 0-9-20-06 HWMA/RCRA Closure Plan for the TRA/MTR Warm Waste System Voluntary Consent Order SITE-TANK-005 Tank System TRA-007  

SciTech Connect

This Hazardous Waste Management Act/Resource Conservation and Recovery Act closure plan was developed for portions of the Test Reactor Area/Materials Test Reactor Warm Waste System located in the Materials Test Reactor Building (TRA-603) at the Reactor Technology Complex, Idaho National Laboratory Site, to meet a further milestone established under Voluntary Consent Order Action Plan SITE-TANK-005 for Tank System TRA-007. The reactor drain tank and canal sump to be closed are included in the Test Reactor Area/Materials Test Reactor Warm Waste System. The reactor drain tank and the canal sump were characterized as having managed hazardous waste. The reactor drain tank and canal sump will be closed in accordance with the interim status requirements of the Hazardous Waste Management Act/Resource Conservation and Recovery Act as implemented by the Idaho Administrative Procedures Act 58.01.05.009 and 40 Code of Federal Regulations 265. This closure plan presents the closure performance standards and methods for achieving those standards.

Winterholler, K.

2007-01-31

356

Dob1p (Mtr4p) is a putative ATP-dependent RNA helicase required for the 3' end formation of 5.8S rRNA in Saccharomyces cerevisiae.  

PubMed Central

The temperature-sensitive mutation, dob1-1, was identified in a screen for dependence on overexpression of the yeast translation initiation factor eIF4B (Tif3p). Dob1p is an essential putative ATP-dependent RNA helicase. Polysome analyses revealed an under accumulation of 60S ribosomal subunits in the dob1-1 mutant. Pulse-chase labelling of pre-rRNA showed that this was due to a defect in the synthesis of the 5.8S and 25S rRNAs. Northern and primer extension analyses in the dob1-1 mutant, or in a strain genetically depleted of Dob1p, revealed a specific inhibition of the 3' processing of the 5.8S rRNA from its 7S precursor. This processing recently has been attributed to the activity of the exosome, a complex of 3'-->5' exonucleases that includes Rrp4p. In vivo depletion of Dob1p also inhibits degradation of the 5' external transcribed spacer region of the pre-rRNA. A similar phenotype was observed in rrp4 mutant strains and, moreover, the dob1-1 and rrp4-1 mutations show a strong synergistic growth inhibition. We propose that Dob1p functions as a cofactor for the exosome complex that unwinds secondary structures in the pre-rRNA that otherwise block the progression of the 3'-->5' exonucleases.

de la Cruz, J; Kressler, D; Tollervey, D; Linder, P

1998-01-01

357

Ultrasonic tissue characterization of the upper trapezius muscle in patients with myofascial pain syndrome.  

PubMed

Myofascial trigger points (MTrPs) are palpable, tender nodules in skeletal muscle that produce symptomatic referred pain when palpated. MTrPs are characteristic findings in myofascial pain syndrome (MPS). The role of MTrPs in the pathophysiology of MPS is unknown. Objective characterization and quantitative measurement of the properties of MTrPs can improve their localization and diagnosis, as well as lead to clinical outcome measures. MTrPs associated with soft tissue neck pain are often found in the upper trapezius muscle. We have previously demonstrated that MTrPs can be visualized using ultrasound imaging. The goal of this study was to evaluate whether texture-based image analysis can differentiate structural heterogeneity of symptomatic MTrPs and normal muscle. PMID:23366899

Turo, Diego; Otto, Paul; Shah, Jay P; Heimur, Juliana; Gebreab, Tadesse; Armstrong, Katherine; Gerber, Lynn H; Sikdar, Siddhartha

2012-01-01

358

Methylenetetrahydrofolate reductase gene polymorphisms in 13 Chinese ethnic populations.  

PubMed

It has been shown that the polymorphisms of Methylenetetrahydrofolate reductase (MTHFR) gene are associated with susceptibility to several disorders including hyperhomocysteinemia, vascular disease, birth defect, and certain cancers, and exhibit great diversities among various populations. The aim of this study was to investigate the prevalence of two common non-synonymous single nucleotide polymorphisms (i.e., C677T and A1298C) at MTHFR gene in 13 Chinese populations. A total of 1015 healthy individuals from 13 populations distributed widely from north to south in China were studied. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism. For C677T polymorphism, the frequency in Chinese of CC homozygous was 42.4%; CT heterozygous was 49.8%; and TT homozygous was 7.9%. For A1298C, AA homozygous was 39.2%; AC heterozygous was 38.6%; and CC homozygous was 22.2%. The allelic frequency of 677T and 1298C was 32.8 and 41.5%, respectively, and each allele frequency had significant variance in 13 Chinese populations. The frequency of the 677T allele among southern populations was 30.7% compared to 38.0% among northeastern and 30.5% among northwestern populations. The difference was statistically significant (p < 0.01). The frequency of 1298C mutation in southerns was 58.9% whereas in northeasterns it was 24.0% and 37.6% in northwesterns. This was also statistically significant (p < 0.01). The MTHFR C677T and A1298C sites were in linkage disequilibrium in the Chinese population revealed by our data. PMID:18098118

Mao, Renfang; Fan, Yihui; Chen, Feng; Sun, Donglin; Bai, Jing; Fu, Songbin

2008-04-01

359

Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: a meta-analysis based on 17 case-control studies.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, is thought to be involved in the development of nonsyndromic orofacial clefts (NSOC). However, conflicting results have been achieved when evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms and the risk of NSOC. To obtain more precise estimations of these associations, a meta-analysis recruiting 17 case-control studies was performed. Among Asians we found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T variant could contribute to elevated risks of NSOC, compared with CC wild-type homozygote (OR=1.741, 95% CI=1.043-2.907 for CT vs. CC, OR=2.311, 95% CI=1.313-4.041 for TT vs. CC, and OR=1.740, 95% CI=1.051-2.882 for CT/TT vs. CC, respectively). Similar effect was also observed on MTHFR 677T T allele, when using C allele as a reference in Asians (OR=1.420, 95% CI=1.191-1.693, for T allele vs. C allele). Furthermore, in stratified analysis by types of disease, CT/CC was suggested to confer decreased susceptibility to CL/P under recessive genetic model (OR=0.854, 95% CI=0.730-1.000). For MTHFR A1298C, the MTHFR 1298C allele in the case group of Caucasians was significantly lower than that in the control group, suggesting a protective effect against NSOC in Caucasian populations (OR=0.711, 95% CI=0.641-0.790, for C allele vs. A allele). In conclusion, the meta-analysis provided confirmative evidences that infants' MTHFR C677T and A1298C polymorphisms were involved in the development of NSOC. PMID:22847888

Pan, Yongchu; Zhang, Weibing; Ma, Junqing; Du, Yifei; Li, Dandan; Cai, Qi; Jiang, Hongbing; Wang, Meilin; Zhang, Zhengdong; Wang, Lin

2012-07-27

360

Correlation of methylenetetrahydrofolate reductase polymorphisms with homocysteine metabolism in healthy Lebanese adults.  

PubMed

Hyperhomocysteinemia is associated with several vascular and teratogenic conditions. Determinants of total homocysteine concentrations include genetic and nutritional factors. This study assesses the relation between homocysteine concentrations and MTHFR gene polymorphisms at two common alleles (C677T (rs1801133) and A1298C (rs1801131)) as well as other predictors of homocysteine (folate, vitamin B(12), body mass index (BMI), age, and gender) in a group of healthy Lebanese: 109 males and 124 females aged 17-55years. We used serum for the determination of homocysteine, folate and vitamin B(12) levels and blood drawn in EDTA tubes for molecular analysis of MTHFR polymorphisms. Hyperhomocysteinemia was present in 59/233 (25.3%) of the subjects, with male/female ratio of 1.95. Multivariable regression analysis showed that homocysteine levels were negatively related to folate and vitamin B(12) and positively related to male gender and C677T homozygosity; but not A1298C polymorphism, BMI or age. The prevalence of wild, heterozygous, and homozygous C677T genotypes was 45.0%, 43.3% and 11.6%, respectively; with a carrier frequency of 54.9% and allelic frequency of 33.3%. The A1298C genotypic prevalence was 39.5%, 30.9%, and 29.6% respectively; with a carrier frequency of 60.5% and allelic frequency of 45.1%. C677T/A1289C compound heterozygosity was present in 47/233 (20.2%) of volunteers. In this first pilot study, gender, folate, vitamin B(12) and C677T mutational status could explain around 32% of homocysteine variations. Future larger studies are recommended to investigate other predictors of homocysteine variation and combine them with markers explored in this and other studies, in order to evaluate their impact on vascular and/or congenital diseases. PMID:22652272

Mahfouz, Rami A; Cortas, Najwa K; Charafeddine, Khalil M; Abdul Khalik, Rabab N; Sarieddine, Doja S; Kadi, Raneem H; Daher, Rose T

2012-05-28

361

5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: a meta-analysis.  

PubMed

There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies investigating an association between the C677T or A1298C polymorphisms and risk of ALL were included. We applied both fixed-effects and random-effects models to combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used to assess publication bias. The meta-analysis of the C677T polymorphism and risk of childhood ALL included 13 studies with a total of 4,894 individuals. Under a fixed-effects model, the TT genotype failed to be associated with a statistically significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI, 0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45; 95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was observed. No association between the A1298C variant and susceptibility to both adult and childhood ALL was disclosed. Our findings support the proposal that the common genetic C677T polymorphism in the MTHFR contributes to the risk of adult ALL, but not to the childhood ALL susceptibility. PMID:17035405

Pereira, Tiago Veiga; Rudnicki, Martina; Pereira, Alexandre Costa; Pombo-de-Oliveira, Maria S; Franco, Rendrik França

2006-10-01

362

MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung.  

PubMed

The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations. PMID:22052259

Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C; Mark, Eugene J; Christiani, David C

2012-01-11

363

Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the southern Spanish population with rheumatoid arthritis.  

PubMed

Abstract Rheumatoid arthritis (RA) is a common illness of global significance for public health. Methotrexate (MTX) is the most broadly used disease-modifying antirheumatic drug for the treatment of RA, but it displays marked person-to-person variation in its propensity for toxicity. Several studies have suggested that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC1) G80A, and ABCB1 C3435T, could be related to methotrexate toxicity. This prospective study examined the different frequencies of MTHFR, RFC1, and ABCB1 pharmacogenetic variations between patients who have RA and those without RA. We also sought to assess the association between these polymorphisms and MTX toxicity. Four single-nucleotide polymorphisms (SNPs) were genotyped: C677T and A1298C from MTHFR, G80A from RFC1, and C3435T from ABCB1. The efficacy and toxicity of MTX were evaluated through clinical follow-up during 1 year of treatment. RA patients showed a higher frequency of the T allele at MTHFR C677T than patients without RA (p=0.049). There was a significant association between the presence of both the T allele at MTHFR C677T (p=0.006), and the C allele at ABCB1 C3435T (p=0.046), with toxicity development after 12 months of MTX treatment. However, there was no correlation between MTX toxicity and either the A allele at MTHFR A1298C or the G allele at RFC1 A80G. These data suggest that the presence of the MTHFR C677T and ABCB1 C3435T SNPs contribute to MTX toxicity in patients with RA. These observations contribute to a rapidly-growing knowledge base on the pharmacogenetics of RA and personalized medicine. PMID:23095111

Plaza-Plaza, José Cristian; Aguilera, Margarita; Cañadas-Garre, Marisa; Chemello, Clarice; González-Utrilla, Alfonso; Faus Dader, María José; Calleja, Miguel Angel

2012-10-24

364

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population.  

PubMed

Major depressive disorder (MDD) is a complex neuropsychiatric disorder where both gene-gene and gene-environment interactions play an important role, but the clues are still not fully understood. One carbon metabolism in the CNS plays a critical role in the synthesis and release of neurotransmitters which are relevant to depressive disorder. We studied genetic polymorphisms of the brain derived neurotrophic factor (BDNF) and the methylenetetrahydrofolate reductase (MTHFR) in association with major depressive disorder. We genotyped the BDNF G196A, the MTHFR C677T, and A1298C polymorphisms in 134 patients diagnosed with major depression and 143 control subjects in Slovak (Caucasian) cohort of patients and probands. We found no significant association of either the BDNF G196A or MTHFR C677T polymorphisms with major depressive disorder neither in female nor male group of patients. However, the MTHFR A1298C genotype distribution was 36.6% (for AA genotype), 48.5% (AC) and 14.9% (CC) for the depressed patients, and 48.9% (AA), 42.7% (AC) and 8.4% (CC), respectively, for the control subjects. Patients with MDD had a higher prevalence of the CC genotype (OR = 2.38; 95% CI = 1.07-5.32; p = 0.032) and the AC + CC genotype (OR = 1.67; 95% CI = 1.03-2.69; p = 0.037) in comparison with the control subjects. This study shows that CC genotype of the MTHFR A1298C is associated with higher risk of MDD in Slovak population. PMID:23255668

Evinova, Andrea; Babusikova, Eva; Straka, Stanislav; Ondrejka, Igor; Lehotsky, Jan

2012-12-01

365

Genetic polymorphisms influence runners' responses to the dietary ingestion of antioxidant supplementation based on pequi oil (Caryocar brasiliense Camb.): a before-after study.  

PubMed

Genes have been implicated in the levels of oxidative stress, lipids, CVD risk, immune reactivity, and performance. Pequi oil (Caryocar brasiliense) has shown anti-inflammatory and hypotensive effects, besides reducing exercise-induced DNA, tissue damages, and anisocytosis. Given that diet can interact with the human genome to influence health and disease, and because genetic variability can influence response to diet, we aim to investigate the influence of 12 gene polymorphisms on inflammatory markers, postprandial lipids, arterial pressure, and plasma lipid peroxidation of runners (N = 125), before and after 14 days of 400 mg pequi-oil supplementation, after races under closely comparable conditions. Arterial pressure was checked before races; blood samples were taken immediately after racing to perform leukogram and plateletgram, Tbars assay, lipid, and CRP dosages and genotyping. CAT, GST-M1/T1, CRP-G1059C, and MTHFR-C677T polymorphisms influenced post-pequi-oil responses in leukogram; Hp and MTHFR-C677T, in plateletgram; Hp, ACE, GSTT1, and MTHFR-A1298C, in lipid profile; MTHFR-A1298C, in C-reactive protein (CRP) levels; and Hp and MnSOD, in Tbars assay. Differences between ACE genotypes in leukogram and total cholesterol disappeared after pequi, and the same occurred for Hp and MnSOD in Tbars assay and for MTHFR-A1298C with CRP levels. Because genetic inheritance is one of the factors that drive atherosclerosis-related lipid abnormalities, results can contribute to a greater understanding of the influence of genetic polymorphisms in situations that push up free radicals. Knowledge is also expanded on how antioxidant supplementation affects an individual's genes and how athletic genetic makeup can affect the way a person responds to antioxidant supplements. PMID:21484158

Miranda-Vilela, Ana Luisa; Lordelo, Graciana Souza; Akimoto, Arthur Kenji; Alves, Penha Cristina Zaidan; Pereira, Luiz Carlos da Silva; Klautau-Guimarães, Maria de Nazaré; Grisolia, Cesar Koppe

2011-04-11

366

Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk.  

PubMed

Functional polymorphisms in genes encoding enzymes involved in folate metabolism might modulate head and neck carcinoma risk because folate participates in DNA methylation and synthesis. We therefore conducted a case-control study of 853 individuals (322 head and neck cancer cases and 531 non-cancer controls) to investigate associations among MTHFR C677T and MTHFR A1298C polymorphisms and head and neck squamous cell carcinoma risk. Interactions between these two polymorphisms and risk factors and clinical histopathological parameters were also evaluated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to genotype the polymorphisms and Chi-square test and multiple logistic regression were used for statistical analyses. The variables age?49 years, male gender, tobacco habits and alcohol consumption, MTHFR 1298 AC or CC genotypes, combined genotypes with two or more polymorphic alleles and 677T and 1298C polymorphic alleles were associated with increased risk for this disease (P<0.05). Furthermore, we found that 1298 AC or CC genotypes were associated with age?49 years, tobacco and alcohol habits (P<0.05). Regarding clinical histopathological parameters, the A1298C polymorphism was more frequent in patients with oral cavity as primary site (P<0.05). MTHFR polymorphisms may contribute for increase risk for head and neck carcinoma and the variables age?49 years, male gender, tobacco and alcohol habits were associated with MTHFR 1298AC or CC genotypes, confirming that individuals with these variables and MTHFR A1298C polymorphism has higher risk for this disease. PMID:21556759

Galbiatti, Ana Lívia Silva; Ruiz, Mariangela Torreglosa; Rodrigues, Juliana Olsen; Raposo, Luiz Sérgio; Maníglia, José Victor; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria

2011-05-10

367

MTHFR Polymorphisms, Folate Intake, and Carcinogen DNA Adducts in the Lung  

PubMed Central

The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin, was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by 32P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced - 111.3% (95% CI, ?3.0 to 360.5%) among 1298AC+CC patients who consumed the lowest level of folate intake as compared with 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations.

Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C.; Mark, Eugene J.; Christiani, David C.

2011-01-01

368

Association of polymorphisms in one-carbon metabolizing genes with breast cancer risk in Syrian women.  

PubMed

Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene. PMID:22373582

Lajin, Bassam; Alhaj Sakur, Amir; Ghabreau, Lina; Alachkar, Amal

2012-02-29

369

Myofascial trigger points and innervation zone locations in upper trapezius muscles  

PubMed Central

Background Myofascial trigger points (MTrPs) are hyperirritable spots located in taut bands of muscle fibres. Electrophysiological studies indicate that abnormal electrical activity is detectable near MTrPs. This phenomenon has been described as endplate noise and it has been purported to be associated MTrP pathophysiology. Thus, it is suggested that MTrPs will be overlap the innervation zone (IZ). The purpose of this work was to describe the location of MTrPs and the IZ in the right upper trapezius. Methods We screened 71 individuals and eventually enrolled 24 subjects with neck pain and active MTrPs and 24 neck pain-free subjects with latent MTrPs. Surface electromyography (sEMG) signals were detected using an electrode matrix during isometric contraction of the upper trapezius. A physiotherapist subsequently examined the subject’s trapezius to confirm the presence of MTrPs and establish their location. IZ locations were identified by visual analysis of sEMG signals. IZ and MTrPs locations were described using an anatomical coordinate system (ACS), with the skin area covered by the matrix divided into four quadrants. Results No significant difference was observed between active and latent MTrPs locations (P = 0.6). Forty-five MTrPs were in the third quadrant of the ACS, and 3 were included in second quadrant. IZs were located approximately midway between the seventh cervical vertebrae and the acromial angle in a limited area in the second and third quadrants. The mean distance between MTrP and IZ was 10.4 ± 5.8 mm. Conclusions According to the acquired results, we conclude that IZ and MTrPs are located in well-defined areas in upper trapezius muscle. Moreover, MTrPs in upper trapezius are proximally located to the IZ but not overlapped.

2013-01-01

370

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

Microsoft Academic Search

Studies investigating the association between gene polymorphisms involved in homocysteine\\/folate metabolism and Down syndrome\\u000a (DS) have reported contradictory or inconclusive results. A meta-analysis of 11 case–control studies relating MTHFR C677T,\\u000a MTHFR A1298C and MTRR A66G gene polymorphisms to the maternal risk of DS was carried out. For MTHFR C677T polymorphism the\\u000a heterogeneity between studies was significant (P = 0.03) and the random

Elias Zintzaras

2007-01-01

371

Polymorphisms in methylenetetrahydrofolate reductase gene ( MTHFR ) and the age of onset of sporadic colorectal adenocarcinoma  

Microsoft Academic Search

Background and aims  Evidence is accumulating for a role of folate in the aetiology of colorectal cancer (CRC). The methylenetetrahydrofolate reductase\\u000a (MTHFR) gene, involved in folate metabolism, is polymorphic in humans. Since it is unknown whether the MTHFR C677T and A1298C polymorphisms alter the risk for CRC, this was the aim of our study.\\u000a \\u000a \\u000a \\u000a Materials and methods  Genomic DNA from 102 sporadic

Carmen S. P. Lima; Helvia Nascimento; Luciana C. Bonadia; Maria T. Teori; Claudio S. R. Coy; Juvenal R. N. Góes; Fernando F. Costa; Carmen S. Bertuzzo

2007-01-01

372

Bilateral transverse sinus thrombosis secondary to a homozygous C677T MTHFR gene mutation.  

PubMed

We describe the case of a previously healthy young man who presented with headache, diplopia, nausea, vomiting, and bilateral papilledema. Magnetic resonance venography of the brain revealed thrombosis of the right transverse sinus. Blood tests showed elevated homocysteine levels, and coagulation studies revealed a homozygous C677T mutation and a heterozygous A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. The patient had no other etiology for venous thrombosis. We recommend screening patients who present with sinus thrombosis for MTHFR gene mutations. PMID:18666857

Kanaan, Ziad M; Mahfouz, Rami; Taher, Ali; Sawaya, Raja A

2008-09-01

373

Methylenetetrahydrofolate reductase gene polymorphisms association with the risk of follicular lymphoma: a meta-analysis.  

PubMed

To date, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and follicular lymphoma have provided controversial results. To clarify the effect of MTHFR polymorphisms on the risk of follicular lymphoma, a meta-analysis of all case-control studies was performed. The fixed effects and random effects model showed that the C677T polymorphism was associated with a risk of follicular lymphoma among Caucasian populations, and A1298C polymorphism was associated with a risk of follicular lymphoma among Asian populations. Our pooled data suggest evidence for a major role of MTHFR polymorphisms in the carcinogenesis of follicular lymphoma. PMID:23359274

Xu, Jing-Yan; Sun, Yun-Yu; Zhou, Min; Wang, Jing; Zhang, Qi-Guo; Xu, Xi-Hui; Zeng, Hui; Ouyang, Jian

2013-01-29

374

Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)  

PubMed Central

Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Methods Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. Results The plasma Hcy level was higher in NAFLD patients compared to the control group (p?=?0.0341). No statistical difference for genotypes 677C/T (p?=?0.110) and 1298A/C (p?=?0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p?=?0.694 and 1298 A/C p?=?0.188). The group of patients and controls showed a statistically significant difference (p?A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT?=?4.44%) (p?>?0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.

2013-01-01

375

Migraine and Genetic Polymorphisms: An Overview  

PubMed Central

The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), ?-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine.

Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

2012-01-01

376

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population  

PubMed Central

Background Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. Methods We evaluated the role of the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking). Conclusions The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

2011-01-01

377

Rapid electron exchange between surface-exposed bacterial cytochromes and Fe(III) minerals  

PubMed Central

The mineral-respiring bacterium Shewanella oneidensis uses a protein complex, MtrCAB, composed of two decaheme cytochromes, MtrC and MtrA, brought together inside a transmembrane porin, MtrB, to transport electrons across the outer membrane to a variety of mineral-based electron acceptors. A proteoliposome system containing a pool of internalized electron carriers was used to investigate how the topology of the MtrCAB complex relates to its ability to transport electrons across a lipid bilayer to externally located Fe(III) oxides. With MtrA facing the interior and MtrC exposed on the outer surface of the phospholipid bilayer, the established in vivo orientation, electron transfer from the interior electron carrier pool through MtrCAB to solid-phase Fe(III) oxides was demonstrated. The rates were 103 times higher than those reported for reduction of goethite, hematite, and lepidocrocite by S. oneidensis, and the order of the reaction rates was consistent with those observed in S. oneidensis cultures. In contrast, established rates for single turnover reactions between purified MtrC and Fe(III) oxides were 103 times lower. By providing a continuous flow of electrons, the proteoliposome experiments demonstrate that conduction through MtrCAB directly to Fe(III) oxides is sufficient to support in vivo, anaerobic, solid-phase iron respiration.

White, Gaye F.; Shi, Zhi; Shi, Liang; Wang, Zheming; Dohnalkova, Alice C.; Marshall, Matthew J.; Fredrickson, James K.; Zachara, John M.; Butt, Julea N.; Richardson, David J.; Clarke, Thomas A.

2013-01-01

378

Leber Hereditary Optic Neuropathy: Do Folate Pathway Gene Alterations Influence the Expression of Mitochondrial DNA Mutation?  

PubMed Central

Background: Leber hereditary optic neuropathy (LHON) is an inherited form of bilateral optic atrophy leading to the loss of central vision. The primary cause of vision loss is mutation in the mitochondrial DNA (mtDNA), however, unknown secondary genetic and/or epigenetic risk factors are suggested to influence its neuropathology. In this study folate gene polymorphisms were examined as a possible LHON secondary genetic risk factor in Iranian patients. Methods: Common polymorphisms in the MTHFR (C677T and A1298C) and MTRR (A66G) genes were tested in 21 LHON patients and 150 normal controls. Results: Strong associations were observed between the LHON syndrome and C677T (P= 0.00) and A66G (P= 0.00) polymorphisms. However, no significant association was found between A1298C (P =0.69) and the LHON syndrome. Conclusion: This is the first study that shows MTHFR C677T and MTRR A66G polymorphisms play a role in the etiology of the LHON syndrome. This finding may help in the better understanding of mechanisms involved in neural degeneration and vision loss by LHON and hence the better treatment of patients.

Aleyasin, A; Ghazanfari, M; Houshmand, M

2010-01-01

379

DNA methylation and sensitivity to antimetabolites in cancer cell lines.  

PubMed

The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to anti-metabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification. The susceptibility of the cancer cell lines to seven antimetabolites was then determined. Cells homozygous for CC at MTHFR-A1298C were significantly more sensitive to cyclocytidine, cytarabine (AraC) and floxuridine than those with AA or AC (p=0.0215, p=0.0166, and p=0.0323, respectively), and carried more methylated tumor suppressor genes (p=0.0313). Among the 12 tumor suppressor genes which were methylated in >25% of cancer cell lines, the methylation status of TIMP3, APC and IGSF4 significantly correlated with sensitivity to pyrimidine synthesis inhibitors. In particular, cells with methylated TIMP3 had reduced mRNA levels and were significantly more sensitive to aphidicolin-glycinate, AraC and 5-FU than cells with unmethylated TIMP3. We speculate that MTHFR-A1298C homozygous CC might direct the methylation rather than the synthesis of DNA, and result in the methylation of several tumor suppressor genes such as TIMP3. These genes could be useful biological markers for predicting the efficacy of antimetabolites. PMID:18202788

Sasaki, Shin; Kobunai, Takashi; Kitayama, Joji; Nagawa, Hirokazu

2008-02-01

380

Metabolic and genetic risk factors for migraine in children.  

PubMed

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation. PMID:16686913

Bottini, F; Celle, M E; Calevo, M G; Amato, S; Minniti, G; Montaldi, L; Di Pasquale, D; Cerone, R; Veneselli, E; Molinari, A C

2006-06-01

381

The Methylenetetrahydrofolate Reductase C677T Polymorphism Influences Risk of Esophageal Cancer in Chinese.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism. This study with 381 esophageal cancer patients and 432 healthy controls was conducted to examine the association of MTHFR C677T and A1298C polymorphisms with susceptibility to esophageal cancer (EC) in a Chinese population. Compared with the CC genotype of MTHFR C677T, subjects carrying homozygote TT and variant genotypes (CT+TT) demonstrated reduced risk of EC with adjusted ORs (95% CI) of 0.44 (0.28-0.71) and 0.57 (0.37-0.88), respectively. However, no association was found between the MTHFR A1298C polymorphism and the risk of EC. Comparing to haplotype CA, haplotypes TA and TC could reduce the susceptibility to EC with adjusted ORs (95% CI) of 0.61(0.47-0.79) and 0.06 (0.01-0.43), respectively. In conclusion, the present study suggested that the MTHFR C677T polymorphism can markedly influence the risk of EC in Chinese. PMID:23803097

Qu, Hong-Hong; Cui, Li-Hong; Wang, Ke; Wang, Peng; Song, Chun-Hua; Wang, Kai-Juan; Zhang, Jian-Ying; Dai, Li-Ping

2013-01-01

382

Genetic polymorphisms of MTHFR and aberrant promoter hypermethylation of the RASSF1A gene in bladder cancer risk in a Chinese population.  

PubMed

Epidemiological studies have shown that folate deficiency increases the risk of cancer by affecting DNA repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. In this study, it was hypothesized that MTHFR (C677T and A1298C) polymorphisms would be associated with bladder cancer and also with hypermethylation of the promoter of the Ras association domain family 1A (RASSF1A) gene. This hospital-based, case-control study of 312 bladder cancer patients and 325 cancer-free controls found that individuals carrying the MTHFR 677TT genotype had a 2.00-fold increased risk of bladder cancer compared with those carrying the 677CC genotype. None of the MTHFR A1298C polymorphisms alone were associated with bladder cancer, but the combined haplotype 677TT/1298AA was associated with a 2.27-fold increased risk compared with haplotype 677CC/1298AA. There was no association between MTHFR gene variants and methylation status of the RASSF1A gene in the 45 bladder cancer patients in whom this was studied. It is concluded that the MTHFR 677TT genotype and the TTAA haplotype may increase the risk of bladder cancer. PMID:20146887

Cai, D W; Liu, X F; Bu, R G; Chen, X N; Ning, L; Cheng, Y; Wu, B

383

Polymorphisms in the CBS gene and homocysteine, folate and vitamin B12 levels: association with polymorphisms in the MTHFR and MTRR genes in Brazilian children.  

PubMed

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) and cystathionine beta-synthase (CBS) genes, involved in the intracellular metabolism of homocysteine (Hcy), can result in hyperhomocysteinemia. The objective of this study was to evaluate prevalence estimates of CBS T833C, G919A and the insertion of 68-bp (844ins68) polymorphisms and their correlation with Hcy, folate and B(12) in 220 children previously genotyped for MTHFR C677T, A1298C, and MTRR A66G. The prevalence of heterozygote children for 844ins68 was 19.5%. The T833C CBS mutation was identified in association with 844ins68 in all the carriers of the insertion. Genotyping for CBS G919A mutation showed that all the children presented the GG genotype. Analysis of Hcy, B(12) and folate, according to the combination of the different genotypes of the C677T and A1298C MTHFR, A66G MTRR, and 844ins68 CBS showed that the 677TT/1298AA/68WW genotype is associated with an increase in Hcy, when compared to the 677CC/1298AC/68WW (P = 0.033) and the 677CT/1298AA/68WW genotypes (P = 0.034). Since B(12) and folate were not different between these groups, a genetic interaction between diverse polymorphisms probably influences Hcy. Our results emphasize the role of genetic interactions in Hcy levels. PMID:18792976

Aléssio, Ana C M; Siqueira, Lúcia H; Bydlowski, Sérgio P; Höehr, Nelci F; Annichino-Bizzacchi, Joyce M

2008-10-15

384

Genetic Background of Nontraumatic Osteonecrosis of the Femoral Head in the Korean Population  

PubMed Central

Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05–3.81) and 1.96 (95% confidence interval, 1.07–3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations. Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Chang, Jun-Dong; Lee, Sang-Soo; Yoo, Je-Hyun; Lee, Kyu Man

2008-01-01

385

Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population.  

PubMed

Major thrombophilic mutations have been identified as risk factors for nontraumatic osteonecrosis of the femoral head (ONFH) in Caucasians. We asked whether the genetic background of patients with ONFH in the Korean population was similar. We analyzed factor V G1691A mutation (factor V Leiden), prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in 71 patients (53 men, 18 women) with ONFH. We classified these patients as 51 alcohol-induced, 18 idiopathic, one steroid-induced, and one dysbaric. We recruited 200 normal control subjects (128 men, 72 women). We used multiplex PCR/restriction fragment length polymorphism for each genotyping. We observed neither factor V Leiden nor prothrombin G20210A mutation. Although methylenetetrahydrofolate reductase A1298C genotypes were not associated with osteonecrosis, methylenetetrahydrofolate reductase C677T variant genotypes increased the risk of ONFH compared with 677CC. Odds ratios of 677CT and 677CT+TT were 2.00 (95% confidence interval, 1.05-3.81) and 1.96 (95% confidence interval, 1.07-3.59), respectively, compared with 677CC. Our data suggest methylenetetrahydrofolate reductase C677T polymorphism plays a role in the pathogenesis of osteonecrosis in the Korean population. It also implies the genetic risk profile of ONFH may differ among ethnic populations. PMID:18350352

Chang, Jun-Dong; Hur, Mina; Lee, Sang-Soo; Yoo, Je-Hyun; Lee, Kyu Man

2008-03-19

386

Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans  

PubMed Central

Prostate cancer (PC) is the second leading cause of cancer death in men. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk; however, empirical data are lacking. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center between 2004–2009 were enrolled into a case-control study. Intake of folate, vitamin B12, B6, and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants, and prostate cancer. Higher dietary methionine intake was associated with PC risk (OR = 2.1; 95%CI 1.1–3.9) The risk was most pronounced in men with Gleason sum <7 (OR = 2.75; 95%CI 1.32– 5.73). The association of higher methionine intake and PC risk was only apparent in men who carried at least one MTHFR A1298C allele (OR = 6.7; 95%CI = 1.6–27.8), compared to MTHFR A1298A noncarrier men (OR = 0.9; 95%CI = 0.24–3.92) (p-interaction = 0.045). There was no evidence for associations between B vitamins (folate, B12, and B6) and PC risk. Our results suggest that carrying the MTHFR A1298C variants modifies the association between high methionine intake and PC risk. Larger studies are required to validate these findings.

Vidal, Adriana C.; Grant, Delores J.; Williams, Christina D.; Masko, Elizabeth; Allott, Emma H.; Shuler, Kathryn; McPhail, Megan; Gaines, Alexis; Calloway, Elizabeth; Gerber, Leah; Chi, Jen-Tsan; Freedland, Stephen J.; Hoyo, Cathrine

2012-01-01

387

Genetic polymorphisms of methylenetetrahydrofolate reductase and colorectal cancer and adenoma.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA methylation and synthesis. Two functional, common polymorphisms (C677T and A1298C) are known in the MTHFR gene. MTHFR activity is lowered in individuals with the 677TT genotype and is somewhat reduced in those with the 1298CC genotype. We reviewed the consistency of reported associations of these polymorphisms with colorectal cancer and adenoma with consideration of the effects of nutritional status. A total of 16 studies have addressed the association between MTHFR C677T polymorphism and colorectal cancer in 10 countries. Decreased risk of colorectal cancer associated with the 677TT genotype has fairly consistently been observed, with few exceptions. This decrease was observable in people with either high or low folate status. Alteration in the thymidylate pool associated with MTHFR activity is postulated as an underlying mechanism. Studies on the A1298C polymorphism are limited, and their results are variable. Almost all of seven studies of colorectal adenoma have found no association between C677T polymorphism and adenoma, but the 677TT genotype seems to be related to increased risk when folate status is poor. Reduced availability of methyl groups for DNA methylation might be more relevant to adenoma formation. Although the underlying mechanisms still remain to be clarified, epidemiological findings regarding MTHFR C677T polymorphism provide strong evidence that adequate folate status confers protection from colorectal cancer. PMID:16128738

Kono, Suminori; Chen, Kun

2005-09-01

388

MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan allelic discrimination assay in various malignancies. The study population included 115 subjects with chronic myelogenous leukemia (CML), 200 with acute myelogenous leukemia (AML), 196 with multiple myeloma (MM) and 434 healthy control subjects. The frequency of 1298CC was statistically significantly higher in subjects with CML than that of the controls (OR=5.12, 95% CI: 1.75-14.9, P-value=.003). Of note, the frequencies of 677CC/1298CC genotype were statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR=8.8, 3.5, 3.83, P-value=.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T. PMID:17156840

Moon, Hee Won; Kim, Tae Young; Oh, Bo Ra; Min, Hyun Chung; Cho, Han Ik; Bang, Soo Mee; Lee, Jae Hoon; Yoon, Sung Soo; Lee, Dong Soon

2006-12-06

389

Genotyping of two single nucleotide polymorphisms in 5,10-methylenetetrahydrofolate reductase by multiplex polymerase chain reaction and capillary electrophoresis.  

PubMed

Two single nucleotide polymorphisms (SNPs) of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, A1298C and C677T, were widely considered to be related with various neoplasia disorders. We established a simple and effective capillary electrophoresis (CE) method for detection of two SNPs in MTHFR gene simultaneously. DNA samples were amplified by multiplex PCR with universal fluorescence-labeled primer and analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE method was performed using 1.5% hydroxyethyl cellulose in 1× TBE buffer containing 1M urea. The PCR products after SSCP procedure were electrokinetically injected at -10 kV, 30s. Separation voltage was -6 kV and the temperature was set at 20°C. The optimal SSCP-CE method was applied to detect two polymorphisms in MTHFR gene of acute lymphoblastic leukemia (ALL) and attention-deficit/hyperactivity disorder (ADHD) patients. Genotyping results were evaluated in terms of relationships between outcomes for ADHD patients after ALL chemotherapy and ALL disease. The SSCP-CE method and multiplex PCR with universal fluorescence primer were used as the fast technique for screening two SNPs in MTHFR gene, A1298C and C677T. The genotyping data were coincident with DNA sequencing. This SSCP-CE method was found feasible for detecting mutation of MTHFR gene in populations. PMID:20870238

Cheng, Hui-Ling; Chiou, Shyh-Shin; Liao, Yu-Mei; Chen, Yen-Ling; Wu, Shou-Mei

2010-09-08

390

Gender-specific association of methylenetetrahydrofolate reductase gene polymorphisms with sporadic amyotrophic lateral sclerosis.  

PubMed

Studies have revealed that elevated homocysteine levels can cause damage to motor neurons through multiple neurotoxic mechanisms, thus leading to the pathogenesis of amyotrophic lateral sclerosis (ALS). One way by which homocysteine levels are increased in the body is the consequence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. Therefore, to address this question, we studied the MTHFR C677T and A1298C polymorphisms in 437 sporadic ALS (SALS) and 439 healthy controls to learn whether they were associated with SALS. The overall SALS were not associated with MTHFR C677T and A1298C polymorphisms (?(2)=1.378; p=0.502; ?(2)=1.304; p=0.521, respectively). However, when we stratified results in terms of gender, we found that the MTHFR C677T polymorphism (?(2)=6.376; p=0.041), T677T genotype (?(2)=5.508; p=0.019; odds ratio [OR]=2.561; 95% confidence interval [CI]=1.142-5.744), C677C/A1298A (?(2)=5.216; p=0.022; OR=0.424, 95% CI=0.199-0.900), and T677T/A1298A (?(2)=6.639; p=0.010; OR=2.900; 95% CI=1.252-6.717) compound genotypes were associated with SALS in female patients only. Moreover, stratification of SALS according to the onset of disease indicated that there was no association between MTHFR C677T (?(2)=1.565; p=0.457; A1298C ?(2)=3.461; p=0.177) polymorphisms and overall spinal onset SALS. Further stratification analysis according to gender revealed that there was a remarkable association between MTHFR C677T (?(2)=9.728, p=0.008), T677T genotype (?(2)=7.820; p=0.005; OR=3.126; 95% CI=1.361-7.178) and T allele (?(2)=5.000; p=0.025; OR=1.711; 95% CI=1.067-2.745), and T677T/A1298A compound genotype (?(2)=9.108; p=0.003; OR=3.540; 95% CI=1.494-8.387) and spinal onset female SALS only. Likewise, there was also association between MTHFR A1298C polymorphism (?(2)=5.946; p=0.051) and the C1298C genotype (?(2)=5.282; p=0.022; OR=2.524; 95% CI=1.125-5.658), and the C677T/C1298C compound genotype (?(2)=7.155; p=0.007; OR=1.045; 95% CI=0.983-1.112) and bulbar onset SALS only in women. In conclusion, the evidence we provide here clearly shows that MTHFR C677T and A1298C polymorphisms are genetic risk factors for SALS in women in a gender-specific manner whether they are of spinal or bulbar onset. PMID:22385294

Sazci, Ali; Ozel, Mavi Deniz; Emel, Ergul; Idrisoglu, Halil Atilla

2012-03-02

391

Proof of principle for an engineered microbial biosensor based on Shewanella oneidensis outer membrane protein complexes.  

PubMed

Shewanella oneidensis is known for its ability to respire on extracellular electron acceptors. The spectrum of these acceptors also includes anode surfaces. Based on this activity, a versatile S. oneidensis based biosensor strain was constructed in which electricity production can be modulated. Construction started with the identification of a usable rate-limiting step of electron transfer to an anode. Thereafter, the sensor strain was genetically engineered to produce a protein complex consisting of the three proteins MtrA, MtrB and MtrF. This complex is associated to the outer membrane and most probably enables membrane spanning electron transfer. MtrF is an outer membrane cytochrome that catalyzes electron transfer reactions on the cell surface. Under anoxic conditions, wild type cells do not express MtrF but rather MtrC as electron transferring outer membrane cytochrome. Still, our analysis revealed that MtrF compared to MtrC overexpression is less toxic to the cell which gives MtrF a superior position for biosensor based applications. Transcription of mtrA, mtrB and mtrF was linked up to an inducible promoter system, which positively reacts to rising l-arabinose concentrations. Anode reduction mediated by this strain was linearly dependent on the arabinose content of the medium. This linear dependency was detectable over a wide range of arabinose concentrations. The l-arabinose biosensor presented in this study proves the principle of an outer membrane complex based sensing method which could be easily modified to different specificities by a simple change of the regulatory elements. PMID:23584391

Golitsch, Frederik; Bücking, Clemens; Gescher, Johannes

2013-03-22

392

Treatment of myofascial trigger points in patients with chronic shoulder pain: a randomized, controlled trial  

Microsoft Academic Search

BACKGROUND: Shoulder pain is a common musculoskeletal problem that is often chronic or recurrent. Myofascial trigger points (MTrPs) cause shoulder pain and are prevalent in patients with shoulder pain. However, few studies have focused on MTrP therapy. The aim of this study was to assess the effectiveness of multimodal treatment of MTrPs in patients with chronic shoulder pain. METHODS: A

Carel Bron; Arthur de Gast; Jan Dommerholt; Boudewijn Stegenga; Michel Wensing; Rob AB Oostendorp

2011-01-01

393

Integrated infrastructure initiatives for material testing reactor innovations  

Microsoft Academic Search

The key goal of the European FP6 project MTR+I3 was to build a durable cooperation between Material Testing Reactor (MTR) operators and relevant laboratories that can maintain European leadership with updated capabilities and competences regarding reactor performances and irradiation technology.The MTR+I3 consortium was composed of 18 partners with a high level of expertise in irradiation-related services for all types of

Jean Dekeyser; Ludo Vermeeren; Daniel Iracane

2011-01-01

394

Management of myofascial trigger point pain  

Microsoft Academic Search

SummarySuccessful management of myofascial trigger point (MTrP) pain depends on the practitioner finding all of the MTrPs from which the pain is emanating, and then deactivating them by one of several currently used methods. These include deeply applied procedures, such as an injection of a local anaesthetic into MTrPs and deep dry needling (DDN), and superficially applied ones, including an

Peter Baldry

2002-01-01

395

Current studies on myofascial pain syndrome  

Microsoft Academic Search

Recent studies have clarified the nature of myofascial trigger points (MTrPs). In an MTrP region, multiple hyperirritable\\u000a loci can be found. The sensory components of the MTrP locus are sensitized nociceptors that are responsible for pain, referred\\u000a pain, and local twitch responses. The motor components are dysfunctional endplates that are responsible for taut band formation\\u000a as a result of excessive

Ta-Shen Kuan

2009-01-01

396

Referred pain elicited by palpation and by needling of myofascial trigger points: A comparison  

Microsoft Academic Search

Objective: To investigate the occurrence of referred pain (REP) elicited by palpation (Pal-ReP) or by needle injection (Inj-ReP) of myofascial trigger point (MTrP), and to assess the correlated factors, including the pain intensity of an active MTrP and the occurrence of local twitch response (LTR).Design: Correlational study.Patients: Ninety-five patients who were treated with MTrP injections.Intervention: MTrP injections.Main Outcome Measure: Pain

Chang-Zern Hong; Ta-Shen Kuan; Jo-Tong Chen; Shu-Min Chen

1997-01-01

397

Export of detritus and invertebrate from headwater streams: linking mountaintop removal and valley fill coal mining to downstream receiving waters  

EPA Science Inventory

Mountaintop removal and valley fill (MTR/VF) coal mining has resulted in large scale alteration of the topography, reduced forest productivity, and burial of headwater streams in the U.S. Central Appalachians. Although MTR/VF coal mining has occurred for several decades and the ...

398

Serial Magnetization Transfer Imaging in Acute Optic Neuritis  

ERIC Educational Resources Information Center

|In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the…

Hickman, S. J.; Toosy, A. T.; Jones, S. J.; Altmann, D. R.; Miszkiel, K. A.; MacManus, D. G.; Barker, G. J.; Plant, G. T.; Thompson, A. J.; Miller, D.H.

2004-01-01

399

Mill versus Locke: A Liberal Analysis of Mountaintop Removal Mining in Central Appalachia  

Microsoft Academic Search

Recently, President Obama’s Environmental Protection Agency (EPA) administrator announced new regulations that could significantly curtail an extremely controversial method of surface mining called mountaintop removal (MTR). The announcement has been met with praise from environmentalists and other opponents of MTR, and strong condemnation from mining corporations that operate in the Central Appalachian Mountains, a poor region of the U.S. But

Michael Cook

400

ANP COMPRESSOR BUILDING, TRA626, UNDER CONSTRUCTION ALONG EAST WALL OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ANP COMPRESSOR BUILDING, TRA-626, UNDER CONSTRUCTION ALONG EAST WALL OF MTR BUILDING. CAMERA FACES SOUTH. AIR RECEIVING TANKS WERE SET UP AND THE WALLS CONSTRUCTED AROUND THEM. CONNECTIONS BETWEEN THE COMPRESSOR BUILDING AND THE MTR WERE BELOW GROUND. INL NEGATIVE NO. 6089. Unknown Photographer, 6/25/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

401

Interrater reliability in myofascial trigger point examination  

Microsoft Academic Search

The myofascial trigger point (MTrP) is the hallmark physical finding of the myofascial pain syndrome (MPS). The MTrP itself is characterized by distinctive physical features that include a tender point in a taut band of muscle, a local twitch response (LTR) to mechanical stimulation, a pain referral pattern characteristic of trigger points of specific areas in each muscle, and the

Robert D. Gerwin; Steven Shannon; Chang-Zern Hong; David Hubbard; Richard Gevirtz

1997-01-01

402

Structural and functional characteristics of natural and constructed channels draining a reclaimed mountaintop removal and valley fill coal mine  

EPA Science Inventory

Mountaintop removal and valley fill (MTR/VF) coal mining has altered the landscape of the Central Appalachian region in the United States. The goals of this study were to 1) compare the structure and function of natural and constructed stream channels in forested and MTR/VF catch...

403

A new-generation 5-nitroimidazole can induce highly metronidazole-resistant Giardia lamblia in vitro  

PubMed Central

The 5-nitroimidazole (NI) compound C17, with a side chain carrying a remote phenyl group in the 2-position of the imidazole ring, is at least 14-fold more active against the gut protozoan parasite Giardia lamblia than the 5-NI drug metronidazole (MTR), with a side chain in the 1-position of the imidazole ring, which is the primary drug for the treatment of giardiasis. Over 10 months, lines resistant to C17 were induced in vitro and were at least 12-fold more resistant to C17 than the parent strains. However, these lines had ID90 values (concentration of drug at which 10% of control parasite ATP levels are detected) for MTR of >200 ?M, whilst lines induced to be highly resistant to MTR in vitro have maximum ID90 values around 100 ?M (MTR-susceptible isolates typically have an ID90 of 5–12.8 ?M). The mechanism of MTR activation in Giardia apparently involves reduction to toxic radicals by the activity of pyruvate:ferredoxin oxidoreductase (PFOR) and the electron acceptor ferredoxin. MTR-resistant Giardia have decreased PFOR activity, which is consistent with decreased activation of MTR in these lines, but C17-resistant lines have normal levels of PFOR. Therefore, an alternative mechanism of resistance in Giardia must account for these super-MTR-resistant cells.

Dunn, Linda A.; Burgess, Anita G.; Krauer, Kenia G.; Eckmann, Lars; Vanelle, Patrice; Crozet, Maxime D.; Gillin, Frances D.; Upcroft, Peter; Upcroft, Jacqueline A.

2010-01-01

404

MTRETR MAINTENANCE SHOP, TRA653. FLOOR PLAN FOR MEZZANINE: LUNCH AND ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MTR-ETR MAINTENANCE SHOP, TRA-653. FLOOR PLAN FOR MEZZANINE: LUNCH AND CONFERENCE ROOM, STORAGE AREA, OFFICES FOR FOREMEN, STENOS, ENGINEERS, DISPATCHER, WOMEN'S RESTROOM. HUMMEL HUMMEL & JONES 810-MTR-ETR-653-A-12, 2/1958. INL INDEX NO. 532-0653-00-381-102837, REV. 3. - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

405

SOUTH WING, TRA661. WEST SIDE. CAMERA FACING EAST. COVERED STAIRWAY ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH WING, TRA-661. WEST SIDE. CAMERA FACING EAST. COVERED STAIRWAY AND BUILDING END AT LEFT OF VIEW IS TRA-652, ANOTHER MTR OFFICE WING. WEST SIDE OF MTR HIGH BAY BEYOND. INL NEGATIVE NO. HD46-45-2. Mike Crane, Photographer, 4/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

406

Monitoring, Targeting and Reporting: a Pathway to Continuous Improvement in Energy Management  

Microsoft Academic Search

Leading industrial organizations strive for continuous improvement in the efficiency, productivity and performance of their systems. It is important for companies to establish effective processes that monitor and review results against performance targets. BC Hydro's Monitoring, Targeting and Reporting (MT&R) program provides a platform for continuous improvement in energy management for industrial organizations. MT&R is a proven method for measuring

Robert Greenwald; Kevin Wallace

407

Magnetization transfer changes of grey and white matter in Parkinson's disease  

Microsoft Academic Search

Since the attempt to evidence structural brain damage in Parkinson's disease (PD) by conventional magnetic resonance imaging (MRI) is usually disappointing, we have investigated whether the magnetization transfer ratio (MTR) can reflect changes in grey and white matter of PD patients. MTR was quantified in 44 regions of interest (ROIs) in both grey and white matter of 11 non-demented PD

N. Tambasco; G. P. Pelliccioli; P. Chiarini; G. E. Montanari; F. Leone; M. L. Mancini; M. Paciaroni; V. Gallai

2003-01-01

408

Development of metronidazole-resistant lines of Blastocystis sp.  

PubMed

Metronidazole (MTR) is frequently used for the treatment of Blastocystis infections, but with variable effectiveness, and often with treatment failures as a possible result of drug resistance. We have developed two Blastocystis MTR-resistant (MTR(R)) subtype 4 WR1 lines (WR1-M4 and WR1-M5), with variable susceptibility to a panel of anti-protozoal agents including various 5-nitroimidazoles, nitazoxanide and furazolidone. WR1-M4 and WR1-M5 were developed and assessed over an 18-month period and displayed persistent MTR resistance, being more than 2.5-fold less susceptible to MTR than the parent isolate. The MTR(R) lines grew with a similar g time to WR1, but were morphologically less consistent with a mixture of size. All Blastocystis isolates and the MTR(R) lines were most susceptible to the 5-nitroimidazole drug ronidazole. WR1-M5 was apparently cross-resistant to satranidazole and furazolidone, and WR1-M4 was cross-resistant to nitazoxanide. These MTR(R) lines now provide a valuable tool for the continued assessment of the efficacy and mechanism of action of new and established drugs against a range of Blastocystis sp. subtypes, in order to identify a universally effective drug and to facilitate understanding of the mechanisms of drug action and resistance in Blastocystis. PMID:22362365

Dunn, L A; Tan, K S W; Vanelle, P; Juspin, T; Crozet, M D; Terme, T; Upcroft, P; Upcroft, J A

2012-02-24

409

FAST CHOPPER BUILDING, TRA665. CONTEXTUAL VIEW: CHOPPER BUILDING IN CENTER. ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FAST CHOPPER BUILDING, TRA-665. CONTEXTUAL VIEW: CHOPPER BUILDING IN CENTER. MTR REACTOR SERVICES BUILDING,TRA-635, TO LEFT; MTR BUILDING TO RIGHT. CAMERA FACING WEST. INL NEGATIVE NO. HD42-1. Mike Crane, Photographer, 3/2004 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

410

Amaurosis fugax: associations with heritable thrombophilia.  

PubMed

The aim of this study was to prospectively assess associations between amaurosis fugax, inherited thrombophilia, and acquired thrombophilia. Thrombophilia and hypofibrinolysis were studied in 11 cases (eight women, three men; all white) with amaurosis fugax, 57 +/- 17 years old, selected by the absence of abnormal brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), magnetic resonance venography (MRV), ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus. Cases were compared to 78 healthy adult white controls (53 +/- 18 years old) for serologic measures, and by polymerase chain reaction to 248 healthy white controls (78 adults, 170 children) for gene mutations. All 11 cases had one or more familial thrombophilic coagulation disorder including one heterozygous for the G1691A factor V Leiden mutation, two with low free protein S, four with high factor VIII, three with resistance to activated protein C, three homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) mutation, two compound C677T-A1298C MTHFR heterozygotes, and three with hypofibrinolytic 4G4G homozygosity for the PAI-1 gene. The case with factor VIII of 160% had two other thrombophilias (compound MTHFR C677T-A1298C heterozygosity, resistance to activated protein C), and hypofibrinolytic high Lp(a). Thrombophilic C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in five of 10 (50%) cases vs. 30 of 248 (12%) controls, Fisher's p (p(f)) = .005. Thrombophilic factor VIII was high in four of 10 (40%) cases vs. 0 of 38 controls, p(f) = .001. Thrombophilic hyperestrogenemia in five of the eight women (four exogenous estrogen, one pregnant) may have interacted with inherited thrombophilia-hypofibrinolysis, promoting thrombus formation. In cases selected by the absence of abnormal brain magnetic resonance imaging, significant ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus, we speculate that amaurosis fugax can be caused by reversible (by anticoagulation) retinal artery thrombi associated with heritable thrombophilia and/or hypofibrinolysis, often augmented by estrogen-driven acquired thrombophilia. PMID:16015408

Glueck, C J; Goldenberg, Naila; Bell, Howard; Golnik, Karl; Wang, Ping

2005-07-01

411

Polymorphisms in the MTHFR gene and their possible association with susceptibility to childhood acute lymphocytic leukemia in an Indian population.  

PubMed

Acute lymphocytic leukemia (ALL) is the most common pediatric cancer worldwide, and is particularly more common in the Indian population. Hence, research is increasingly examining the factors involved in disease development. In the present study, we examined the effect of MTHFR (5,10-methylenetetrahydrofolate reductase) C677T and A1298C polymorphisms in ALL. Blood samples of 135 children with ALL and 142 matched controls were analysed. The presence of MTHFR C677T and A1298C polymorphisms were screened using polymerase chain reaction-restriction fragment length polymorphism based approaches. The frequency of MTHFR 677CC, 677CT and 677TT genotypes were 37.77%, 57.03% and 5.18% in cases and 55.63%, 40.84% and 3.52% in controls, respectively. Frequencies of MTHFR 1298AA, 1298AC and 1298CC genotypes were 30.37%, 61.48% and 8.14% in cases and 45.77%, 47.88% and 6.33% in controls, respectively. The present study inidcates that there is an association between MTHFR gene polymorphisms and ALL. MTHFR variants also showed a gender bias. The frequencies of MTHFR 677CC and 677CT genotypes were 33.33% and 65.51% in males and 45.83% and 41.66% in females. Frequencies of MTHFR 1298AA, 1298AC and 1298CC genotypes were 26.43%, 67.81% and 5.74% in males and 37.5%, 50.0% and 12.5% in females, respectively. It is evident that the male children were more susceptible to ALL compared to female children. Associations found in these studies were significant with respect to gender bias; hence, it is possible that MTHFR C677T and A1298C can be good markers for ALL. Moreover, the possibility also exists that these variants may be influenced by the folate uptake of mothers during pregnancy, thereby influencing the enzyme activity and the ethnicity of the cases examined to date. The gender bias of MTHFR polymorphism in ALL is reported for the first time. PMID:16923565

Reddy, Haranatha; Jamil, Kaiser

2006-07-01

412

Ultrasonic characterization of the upper trapezius muscle in patients with chronic neck pain.  

PubMed

Myofascial trigger points (MTrPs) are palpable, tender nodules in taut bands of skeletal muscle that are painful on compression. MTrPs are characteristic findings in myofascial pain syndrome (MPS). The role of MTrPs in the pathophysiology of MPS is unknown. Localization, diagnosis, and clinical outcome measures of painful MTrPs can be improved by objectively characterizing and quantitatively measuring their properties. The goal of this study was to evaluate whether ultrasound imaging and elastography can differentiate symptomatic (active) MTrPs from normal muscle. Patients with chronic (>3 months) neck pain with spontaneously painful, palpable (i.e., active) MTrPs and healthy volunteers without spontaneous pain (having palpably normal muscle tissue) were recruited for this study. The upper trapezius muscles in all subjects were imaged, and the echotexture was analyzed using entropy filtering of B-mode images. Vibration elastography was performed by vibrating the muscle externally at 100 Hz. Color Doppler variance imaging was used to quantify the regions of color deficit exhibiting low vibration amplitude. The imaging measures were compared against the clinical findings of a standardized physical exam. We found that sites with active MTrPs (n = 14) have significantly lower entropy (p < 0.05) and significantly larger nonvibrating regions (p < 0.05) during vibration elastography compared with normal, uninvolved muscle (n = 15). A combination of both entropy analysis and vibration elastography yielded 69% sensitivity and 81% specificity in discriminating active MTrPs from normal muscle. These results suggest that active MTrPs have more homogeneous texture and heterogeneous stiffness when compared with normal, unaffected muscle. Our methods enabled us to improve the imaging contrast between suspected MTrPs and surrounding muscle. Our results indicate that in subjects with chronic neck pain and active MTrPs, the abnormalities are not confined to discrete isolated nodules but instead affect the milieu of the muscle surrounding palpable MTrPs. With further refinement, ultrasound imaging can be a promising objective method for characterizing soft tissue abnormalities associated with active MTrPs and elucidating the role of MTrPs in the pathophysiology of MPS. PMID:23493615

Turo, Diego; Otto, Paul; Shah, Jay P; Heimur, Juliana; Gebreab, Tadesse; Zaazhoa, Maryam; Armstrong, Katherine; Gerber, Lynn H; Sikdar, Siddhartha

2013-04-01

413

Bilateral consecutive optic neuropathy in a patient with thrombophilia.  

PubMed

A 39-year-old man was admitted with a sudden visual loss in the left eye. Visual acuities were 10/10 on the right and 1/10 on the left. Fundus examination did not show any abnormalities. Visual acuity improved to 10/10 and visual field defect regressed in the following 2 weeks. Three years later, the patient returned with acute visual loss in the right eye. Visual acuities were 2/10 on the right and 10/10 on the left. Right optic disc had blurred margins with mild oedema. The tests revealed methylenetetrahydrofolate reductase A1298C mutation with positive lupus anticoagulant and hyperhomocysteinaemia. Enoxaparin was initialised with vitamin B12 supplementation. Complete visual recovery occurred in the following 3 weeks in both eyes. Thrombophilic screening seems to be important in the treatment and prevention of an attack in the second eye of patients with non-arteritic anterior ischaemic optic neuropathy. PMID:23771968

Ornek, Nurgül; Onaran, Zafer; Ornek, Kemal; Büyüktortop, Nesrin

2013-06-13

414

[The role of homocysteine and methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase polymorphisms in the development of cardiovascular diseases and hypertension].  

PubMed

Cardiovascular diseases (CVDs) are the leading causes of death in the developed countries. Elevated homocysteine level is as an independent risk factor of CVDs. The C677T and A1298C variants of methylenetetrahydrofolate reductase gene (MTHFR) have been shown to influence folate and homocysteine metabolisms. However, the relationship between MTHFR polymorphisms and hyperhomocysteinemia has not been well established yet. The gene variants were also reported to be associated with CVDs. In addition, the C677T polymorphisms may play a role in the development of hypertension. Recent research evidence has suggested that MTHFR variants might be independently linked to CVDs and hypertension, because of the involvement of the MTHFR enzyme product (5-methyl-tetrahydrofolate /5-MTHF) in the regulation of endothelial functions. Further research is required to investigate the association between gene polymorphisms of folate-metabolizing enzymes and CVDs, and to identify the possible role of the relevant gene variants in the molecular pathogenesis of hyperhomocysteinemia. PMID:22411217

Marosi, Krisztina; Agota, Annamária; Végh, Veronika; Joó, József Gábor; Langmár, Zoltán; Kriszbacher, Ildikó; Nagy, Zsolt B

2012-03-25

415

[Right atrial thrombus: a rare presentation of plasminogen activator inhibitor deficiency].  

PubMed

Free-floating right atrial thrombi are rare but associated with high mortality. Although advances in echocardiography have improved diagnosis, their management is still the subject of debate. A 24-year-old woman with a history of smoking, obesity and oral contraceptive use presented to the emergency department with dyspnea, cough and hemoptysis. Transthoracic echocardiography revealed a large free-floating cardiac mass occupying the right atrial chamber and restricting tricuspid valve opening. In view of recurrent pulmonary embolism, she was referred for cardiac surgery and the cardiac mass was excised. Anatomopathological analysis revealed an organized and calcified thrombus. Genetic study showed her to be homozygous for the 4G/4G allelic variant of plasminogen activator inhibitor-1 and heterozygous for the allelic variant A1298C of 5,10-methylenetetrahydrofolate reductase. PMID:22230099

Cordeiro Piçarra, Bruno; Santos, Ana Rita; Dionísio, Pedro; Vasconcelos, João; Banazol, Nuno; Lourenço, Sílvia; Caetano, Fátima; Jara, António

2012-01-09

416

MTHFR polymorphisms' influence on outcome and toxicity in acute lymphoblastic leukemia patients.  

PubMed

Recently the influence of polymorphisms of different genes involved in metabolism of chemoterapic agents have been studied especially in childhood acute lymphoblastic leukemia (ALL). We evaluated the influence of C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms on time to relapse and survival and on methotrexate (MTX) toxicity in 82 ALL adult patients. Relapse free survival and event free survival between homozygous wild-type and variant patients in both polymorphisms were not significantly different. However, we observed an association between 677TT variant and survival in a subset of ALL patients homogenously treated with MTX-based maintenance (p=0.02). In the same subgroup we confirmed the role of 677TT variant on toxicity during MTX treatment (p=0.003). PMID:17512587

Chiusolo, Patrizia; Reddiconto, Giovanni; Farina, Giuliana; Mannocci, Alice; Fiorini, Alessia; Palladino, Mariangela; La Torre, Giuseppe; Fianchi, Luana; Sorà, Federica; Laurenti, Luca; Leone, Giuseppe; Sica, Simona

2007-05-18

417

Maternal cerebral venous thrombosis, uncommon but serious disorder, pathologic predictors and contribution of prothrombotic abnormalities.  

PubMed

Cerebral venous thrombosis (CVT) is a rare complication during pregnancy or the puerperium. Our aim was to identify thrombotic risk profiles that predispose to maternal CVT.The study comprised 151 individuals. All participants had a thrombotic workup that included the following: genetic markers: factor V Leiden G1691A and G20210A prothrombin mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms; protein assays: protein C, protein S and antithrombin; other tests: blood typing and screening for hyperhomocysteinemia. Maternal CVT has been associated with factor V Leiden, the prothrombin G20210A mutation, protein C deficiency and hyperhomocysteinemia. We also speculate that non-O blood groups and preeclampsia could be independent risk factors for CVT. PMID:23337711

Klai, Sarra; Fekih-Mrissa, Najiba; Mrissa, Ridha; Rachdi, Radhouen; Gritli, Nasredine

2013-04-01

418

Genetic polymorphisms in venous thrombosis and pulmonary embolism after total hip arthroplasty: a pilot study.  

PubMed

Deep venous thrombosis (DVT) after major orthopaedic surgery is a substantial concern. We asked whether the single or combined presence of thrombophilic genetic polymorphisms might further increase the already high risk for venous thrombosis and pulmonary embolism (PE) after THA. We therefore compared the prevalence of factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and plasminogen activator inhibitor 4G/5G polymorphisms between 50 patients with symptomatic DVT within 3 weeks after elective THA and an asymptomatic control group of 85 patients. We found no major difference for the presence of a single mutation between the groups. Factor V Leiden and homozygous MTHFR C667T mutations were of borderline significance with odds ratios (95% confidence intervals) of 3.73 (0.89-15.63) and 2.93 (0.92-9.29), respectively. Patients with homozygous or combined heterozygous status of MTHFR C677T and A1298C mutation had a higher frequency of DVT after elective THA (odds ratio, 2.86; 95% confidence interval, 1.32-6.35) than those with wild-type. The presence of a single mutation may not further increase the already high risk for symptomatic DVT after THA, whereas combinations of mutations of distinct polymorphisms might be important. However, prospective studies with a larger number of patients are needed before we would recommend preoperative screening. Level of Evidence: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18800213

Ringwald, Juergen; Berger, Annika; Adler, Werner; Kraus, Cornelia; Pitto, Rocco P

2008-09-18

419

Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan.  

PubMed

Methylenetetrahydrofolate reductase (MTHFR) balances the pool of folate coenzymes in one-carbon metabolism for DNA synthesis and methylation, both are implicated in carcinogenesis. Two common variants in the MTHFR gene (C677T and A1298C) have been associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate cancer-predisposing factor. To evaluate the C677T and A1298C functional polymorphisms in the MTHFR gene and their associations with breast cancer risk, as well as the potential modifying effect by plasma folate status on the MTHFR-associated risk, a hospital-based case-control study was conducted on a Taiwanese population consisting of 146 histologically confirmed incident breast cancer cases and their 285 age-matched controls without a history of cancer. A PCR-RFLP method was used for MTHFR polymorphism genotyping and RIA was used to measure the plasma folate. Statistical evaluations were performed using logistic regression analysis. The plasma folate level was inversely associated with breast cancer risk with an adjusted odds ratio (OR) of 0.52 [95% confidence interval (CI): 0.26-1.05] observed among women who were in the highest plasma folate tertile. The MTHFR 677T and 1298C variant alleles were associated with decreased risk for breast cancer [adjusted ORs were 0.81 (95% CI: 0.54-1.21) and 0.57 (95% CI: 0.36-0.89) for 677CT + TT genotypes and 1298AC + CC genotypes, respectively]. Furthermore, compound heterozygote and homozygote variants (677CT + TT and 1298AC + CC) had greater reduced risk (adjusted OR: 0.11, 95% CI: 0.03-0.43) among women with lower plasma folate levels. These results provide support for the important role of folate metabolism in breast tumorigenesis. Further mechanistic studies are warranted to investigate how MTHFR combined genotypes exert their effect on cancer susceptibility. PMID:16777985

Chou, Yu-Ching; Wu, Mei-Hsuan; Yu, Jyh-Cherng; Lee, Meei-Shyuan; Yang, Tsan; Shih, Hsiu-Lan; Wu, Tsai-Yi; Sun, Chien-An

2006-06-15