scholarly journals No association between common polymorphisms in genes of folate and homocysteine metabolism and the risk of Down's syndrome among French mothers

2005 ◽  
Vol 94 (2) ◽  
pp. 166-169 ◽  
Author(s):  
Abalo Chango ◽  
Nathalie Fillon-Emery ◽  
Clotilde Mircher ◽  
Henri Bléhaut ◽  
Daniel Lambert ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Methylenetetrahydrofolate Reductase ◽  
Allele Frequencies ◽  
Methionine Synthase ◽  
Reduced Folate Carrier ◽  
French Population ◽  
Maternal Risk ◽  
Methionine Synthase Reductase ◽  
French Case ◽  
Combined Genotypes

The cause of the non-disjunction leading to trisomy 21 remains unclear. Recent evidence has suggested that 5, 10-methylenetetrahydrofolate reductase (MTHFR) and/or methionine synthase reductase (MTRR) might contribute to the maternal risk of trisomy 21. The purpose of the present study was to analyse these findings among the French population and to investigate whether common polymorphisms in genes of the folate and homocysteine pathway, including the MTHFR 677C>T, MTHFR 1298A>C, the methionine synthase (MTR) 2756A>G, the cystathionine β-synthase (CBS) 844Ins68 and the reduced folate carrier (RFC-1) 80G>A polymorphisms, contribute to the risk of trisomy 21. The risk was studied by analysing independent and combined genotypes in 119 case mothers and 119 control mothers. The MTHFR 677T, MTHFR 1298C, MTR2756G, MTRR66G, CBSIns68+ and the RFC-1 80G allele frequencies were not significantly different among French case mothers, compared with control mothers. The risk of having a child with trisomy 21 did not appear to be linked to polymorphisms in genes associated with folate and homocysteine metabolism.

Association of MTRR A66G polymorphism (but not of MTHFR C677T and A1298C, MTR A2756G, TCN C776G) with homocysteine and coronary artery disease in the French population

2005 ◽  
Vol 94 (09) ◽  
pp. 510-515 ◽  
Author(s):  
Yves Juilliére ◽  
Mirande Candito ◽  
Charles E. Adjalla ◽  
Pierre Gibelin ◽  
Bernard Herbeth ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Methionine Synthase ◽  
French Population ◽  
Methionine Synthase Reductase ◽  
Mtrr A66g ◽  
Artery Disease ◽  
The Individual

Summarymethylenetetrahydrofolate reductase polymorphism (MTHFR C677T) is an established determinant of homocysteine plasma level (t-Hcys) while its association with coronary artery disease (CAD) seems to be more limited. In contrast, the association of the substitutions A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR) and C776G of transcobalamin (TCN) to both t-Hcys and CAD needs to be evaluated further. The objective was to evaluate the association of these polymorphisms with t-Hcys and CAD in a French population. We investigated the individual and combined effects of these polymorphisms and of vitamin B12 and folates with t-Hcys in 530 CAD patients and 248 matched healthy controls. t-Hcys was higher in the CAD group than in controls (11.8 vs 10.4 μM, P<0.0001) and in carriers of MTRR AA and MTHFR 677TT than in those carrying the most frequent allele of both polymorphisms (13.8 vs 11.4 μM, P=0.0102 and 12.5 vs 11.0 mM, P=0.0065 respectively). The frequency of MTRR A allele was higher in CAD patients than in controls (0.48 [95% CI: 0.44-0.52] vs 0.38 [95% CI: 0.32-0.44], P=0.0081) while no difference was observed for MTHFR 677T frequency. In multivariate analysis, t-Hcys > median and MTRR AA genotype were two significant independent predictors of CAD with respective odds ratios of 3.1 (95 % CI: 1.8-5.1, P<0.0001) and 4.5 (95% CI: 1.5-13.1, P=0.0051). In conclusion, in contrast to North Europe studies, MTRR AA genotype is a genetic determinant of moderate hyperhomocysteinemia associated with CAD in a French population without vitamin fortification.

scholarly journals Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura

Cephalalgia ◽  
2013 ◽  
Vol 33 (7) ◽  
pp. 469-482 ◽  
Author(s):  
Kathryn A Roecklein ◽  
Ann I Scher ◽  
Albert Smith ◽  
Tamara Harris ◽  
Gudny Eiriksdottir ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Multiple Testing ◽  
Haplotype Analysis ◽  
Methylenetetrahydrofolate Reductase ◽  
Population Based ◽  
Methionine Synthase ◽  
Association Testing ◽  
Methionine Synthase Reductase ◽  
Increased Risk ◽  
Genes Encoding

Aims The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR; EC 2.1.1.13) and methionine synthase reductase ( MTRR; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR, MTR, and MTRR. Methods Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( n = 367), migraine without aura ( n = 85), migraine with aura ( n = 167), and no headache ( n = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing. Results Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing. Conclusions These results suggest that MTRR variants may protect against migraine with aura in an older population.

Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily

2006 ◽  
Vol 96 (08) ◽  
pp. 154-159 ◽  
Author(s):  
Rosa-Maria Guéant-Rodriguez ◽  
Guido Anello ◽  
Rosario Spada ◽  
Antonino Romano ◽  
Adrian Fajardo ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Methionine Synthase ◽  
Italian Population ◽  
Significant Independent Predictor ◽  
Methionine Synthase Reductase ◽  
Ischaemic Cerebrovascular Disease ◽  
Folate And Vitamin B12 ◽  
Neutral Effect

SummaryAssociation between methylenetetrahydrofolate reductase polymorphism (MTHFR 677 C>T), a determinant of homocysteine plasma level (t-Hcys), with ischaemc cerebrovascular disease (iCVD) seems to be neutral in North Europe and North America. The association of 2756 A>G of methionine synthase (MTR), 66 A>G of methionine synthase reductase (MTRR) and 776 C>G of transcobalamin (TCN2) needs to be evaluated further. It was the objective of this study to evaluate the association of these polymorphisms, t-Hcys, vitamin B12 and folate levels with iCVD, in an Italian population from Sicily. We investigated the association of these polymorphisms, t-Hcys, vitamin B12 and folate with iCVD in 252 subjects, including 131 cases and 121 sexand agematched healthy controls. t-Hcys was higher in the iCVD group than in controls [15.3 (11.5–17.9) vs. 11.6 (9.4–14.5) µM; P=0. 0007] and also in subjects withTCN2 776CG genotype, compared to homozygous genotypes [13.5 (9.9± 16.9) vs. 11.7 (9.6 ± 14.4) µM; P=0. 0327]. The folate level in cases and controls was consistent with an adequate dietary intake [12.7 (9.0–15.3) vs. 12.5 (9.6–16.9) nM; P=0. 7203]. In multivariate analysis, t-Hcys was a significant independent predictor of iCVD with an odds ratio of 1.14 (95% C.I. : 1.06–1.24; P=0. 0006). No association was found between MTHFR, MTR, MTRR and TCN2 polymorphisms and iCVD risk. We have found an influence of t-Hcys and a neutral effect of MTHFR, MTR, MTRR and TCN2 on iCVD risk in Sicily. The neutral influence of these polymorphisms may be explained by adequate status in folate and vitamin B12. Other factors underlying the increased t-Hcys need further investigations.

scholarly journals Evaluation of c677t and a1298c polymorphism of the methylenetetrahydrofolate reductase gene as a maternal risk factor for trisomy 21 (a monocentric study)

2017 ◽  
Vol 25 (1) ◽  
pp. 27-35
Author(s):  
Simona Bucerzan ◽  
Radu Anghel Popp ◽  
Raluca Maria Vlad ◽  
Cecilia Lazea ◽  
Radu Nicolaescu ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Control Group ◽  
Healthy Children ◽  
Mthfr Polymorphisms ◽  
Maternal Risk ◽  
Reductase Gene ◽  
A1298c Polymorphism ◽  
Methylenetetrahydrofolate Reductase Gene

Abstract Aim: To assess the risk for trisomy 21 in children, depending on the polymorphisms C677T and A1298C of the methylenetetrahydrofolate reductase (MTHFR) gene in mothers. Methods: For 93 mothers who have children with trisomy 21 and 202 mothers of healthy children (control group), genotyping of MTHFR polymorphisms C677T and A1298C was performed. Results: For each polymorphism, three genotypes were identified (normal homozygous, heterozygous and mutant homozygous). For the polymorphism C677T, the frequencies of the three genotypes (CC, CT and TT) were 50.5%, 40.8% and 8.6% in mothers of children with trisomy 21, versus 42.6%, 46% and 11.4% in mothers of healthy children, with no statistically significant differences. The frequency of the polymorphism A1298C was not statistically significant between the two groups for the genotype (AA) (48.4% vs 56.4%) or the genotype (AC) (39.8% vs 38.6%), but the genotype TT was more frequent in mothers of children with trisomy 21 (11.8% vs 4.9%; p = 0.033; OR = 2.57). Conclusion: Women with genotype CC for the polymorphism A1298C of the MTHFR gene have a 2.57 times higher risk of offspring with trisomy 21.

Genetic polymorphisms of the enzymes involved in DNA methylation and synthesis in elite athletes

2011 ◽  
Vol 43 (16) ◽  
pp. 965-973 ◽  
Author(s):  
Ileana Terruzzi ◽  
Pamela Senesi ◽  
Anna Montesano ◽  
Antonio La Torre ◽  
Giampietro Alberti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Late Phase ◽  
Muscle Growth ◽  
Methionine Synthase ◽  
Control Group ◽  
Dna Hypomethylation ◽  
Methionine Synthase Reductase ◽  
Proliferation And Differentiation

Physical exercise induces adaptive changes leading to a muscle phenotype with enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes' DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT), and 68-bp ins of cystathionine β-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG), and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared with the control group ( P = 0.0001, P = 0.018, and P = 0.0001), suggesting a reduced DNA methylating capacity. We therefore assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6), and late-phase (MHC) of myogenesis in a cellular model of hypomethylated or unhypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells [fold change (FC) = Myf-5: 1.21, 1.35; MyoD: 0.9, 1.47; Myf-6: 1.39, 1.66; MHC: 1.35, 3.10 in GMA, DMA, respectively] compared with the control groups (FC = Myf-5: 1.0, 1.38; MyoD: 1.0, 1.14; Myf-6: 1.0, 1.44; MHC: 1.0, 2.20 in GM, DM, respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS, and MSR enzymes induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass.

scholarly journals The roles of MTRR and MTHFR gene polymorphisms in congenital heart diseases: a meta-analysis

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Aiping Xu ◽  
Weiping Wang ◽  
Xiaolei Jiang
Keyword(s):  
Gene Polymorphisms ◽  
Congenital Heart ◽  
Methylenetetrahydrofolate Reductase ◽  
Heart Diseases ◽  
Meta Analysis ◽  
Mthfr Gene ◽  
Methionine Synthase ◽  
Congenital Heart Diseases ◽  
Methionine Synthase Reductase ◽  
Study Participants

Background: We performed the present study to better elucidate the correlations of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms with the risk of congenital heart diseases (CHD). Methods: Eligible articles were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations of MTHFR and MTRR gene polymorphisms with CHD. Results: A total of 47 eligible studies were finally included in our meta-analysis. Our overall analyses suggested that MTRR rs1801394, MTRR rs1532268, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms were all significantly associated with the risk of CHD in certain genetic models. Further subgroup analyses according to ethnicity of study participants demonstrated that the MTRR rs1801394 polymorphism was significantly correlated with the risk of CHD only in Asians, whereas MTRR rs1532268, MTHFR rs1801133 and MTHFR rs1801131 polymorphisms were significantly correlated with the risk of CHD in both Asians and Caucasians. Conclusions: Our findings indicated that MTRR rs1532268, MTHFR rs1801131 and MTHFR rs1801133 polymorphisms may affect the risk of CHD in Asians and Caucasians, while the MTRR rs1801394 polymorphism may only affect in risk of CHD in Asians.

Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2483-2488 ◽  
Author(s):  
Leo A. J. Kluijtmans ◽  
Ian S. Young ◽  
Colin A. Boreham ◽  
Liam Murray ◽  
Dorothy McMaster ◽  
...  
Keyword(s):  
Young Adults ◽  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Dietary Factors ◽  
Methionine Synthase ◽  
Interactive Effects ◽  
Serum Folate ◽  
Homocysteine Concentration ◽  
Functional Polymorphisms ◽  
Methionine Synthase Reductase

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine β-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B12, and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between theMTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B12. Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.

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