OBJECTIVETo evaluate the associations between polymorphisms of methionine synthase(MTR) A2756G and methionine synthase reductase(MTRR) G66A and risk of coronary artery disease.

METHODSLiteratures in Medline reporting the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease from January 1990 to May 2010 were searched. A total of 14 relevant articles were selected and 13 of them met the criteria. A Meta-analysis was performed to estimate the pooled odds ratio (OR) to evaluate the relationship between polymorphisms of MTR A2756G and MTRR G66A and risk of coronary artery disease. All analyses were performed using the STATA statistical software.

RESULTSAmong the 13 studies, eight case-control studies containing 2143 cases of coronary artery disease and 2270 controls were included in the analysis of MTR A2756G and risk of coronary artery disease. Meanwhile, five case-control studies with 811 cases of coronary artery disease and 387 controls were included in the analysis of MTRR G66A and risk of coronary artery disease. In the analysis of MTRR G66A related to the risk of coronary artery disease, there were 246 GG carries, 397 AG carriers and 168 AA carriers in the group of coronary artery disease, against 102 GG carriers, 203 AG carriers and 82 AA carriers in the control group. Compared with the MTRR GG carriers, the risk of coronary artery disease decreased significantly by 27% (OR = 0.73, 95%CI: 0.54 - 0.99) and 25% (OR = 0.75, 95%CI: 0.56 - 1.00) (Egger's test t = -0.19, P = 0.862) in the MTRR 66 AG and AG/AA carriers, respectively, and also decreased in the MTRR AA carriers but significant difference was observed (OR = 0.84, 95%CI: 0.42 - 1.68). There was no significant association between coronary artery disease and MTR A2756G.

CONCLUSIONThese results suggest that MTRR66 may play a role in coronary artery disease susceptibility. MTRR 66 A allele carries are associated with a statistically significant decreased risk of coronary artery disease susceptibility.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Alleles ; Coronary Artery Disease ; genetics ; Ferredoxin-NADP Reductase ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans

Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index > or = 25 kg/m2), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; Ferredoxin-NADP Reductase ; Folic Acid ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; Odds Ratio ; Oxidoreductases ; Polymorphism, Single Nucleotide ; Stomach Neoplasms

OBJECTIVETo investigate the association of the polymorphisms of methionine metabolism genes and the phenotype of X-linked adrenoleukodystrophy (X-ALD) and clinical severity.

METHODSThe clinical information of 120 X-ALD patients were analyzed and three genetic variants involved in the methionine metabolism, including cystathionine beta-synthase (CBS) c.844_855ins68, 5-methyltetrahydrofolate-homocysteine-S-methyltransferase (MTR) c.2756A to G, and transcobalamin 2 (TC2) c.776 C to G were analyzed by polymerase chain reaction and sequencing. The association between these polymorphisms and phenotype of X-ALD was studied.

RESULTSThe frequency of GG genotype of the TC2 c.776 C/G was higher in patients with central nervous system(CNS) demyelination than in controls (P= 0.012). However, the other two polymorphisms did not show any significant associations with the phenotypes.

CONCLUSIONThe GG genotype of TC2 c.776 C/G may contribute to X-ALD phenotype.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Adrenoleukodystrophy ; genetics ; Cystathionine beta-Synthase ; genetics ; Gene Frequency ; Genotype ; Humans ; Male ; Methionine ; metabolism ; Phenotype ; Polymorphism, Genetic ; Transcobalamins ; genetics

OBJECTIVETo study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Chinese.

METHODSNinety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method.

RESULTSThere was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0.36-1.79) and 1.26(0.54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0.88(0.49-1.75), and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (chi-square=0.034,P>0.05). The results of haplotype-based haplotype relative risk (HHRR) analysis (chi-square=0.03,P>0.05) and family-based association tests (FBAT) (Z=0.186, P>0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P.

CONCLUSIONThe A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Asian Continental Ancestry Group ; genetics ; Child ; Cleft Lip ; genetics ; Cleft Palate ; genetics ; Female ; Genotype ; Humans ; Male ; Polymorphism, Genetic

OBJECTIVE: Spermatogenesis is a complex process that is regulated by a number of genes, some of which are involved in folate-dependent 1-carbon metabolism. Methionine synthase (encoded by MTR) is a key enzyme participating in this pathway. This study aimed to investigate the relationship of the MTR 2756A > G polymorphism with idiopathic male fertility in the Iranian population. METHODS: The participants of this study included 100 men with idiopathic infertility and 100 healthy men as the control group. Genotyping of MTR 2756A > G was performed using the polymerase chain reaction and restriction fragment length polymorphism technique. The obtained data were analyzed using SPSS ver. 20.0 with a level of confidence of p< 0.05. RESULTS: The frequencies of the A and G alleles at this locus were 77% and 23% in infertile patients and 84% and 16% in the control group, respectively. The frequencies of the GG, GA, and AA genotypes were 5%, 36%, and 59% in the infertile patients versus 3%, 27%, and 70% in the control group, respectively. No significant difference was observed in any genetic models. CONCLUSION: In general, the findings of this study suggest that the MTR 2756A > G single-nucleotide polymorphism is not a predisposing factor for idiopathic infertility in men.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; Alleles ; Causality ; Fertility ; Genotype ; Humans ; Infertility ; Infertility, Male ; Male ; Male ; Metabolism ; Methionine ; Models, Genetic ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Spermatogenesis

Hyperhomocysteinemia is known to be associated with an increased risk of myocardial infarction, stroke, peripheral arterial disease, and venous thrombosis. Gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) may account for reduced enzyme activity and hyperhomocysteinemia. A recent study has documented evidence of polygenic regulation of plasma homocyteine. We report here on a case of occlusive stroke at young age and hyperhomocysteinemia with homozygous VN (677C to T) variant in the MTHFR gene as well as homozygous D/D (2756G to A) variant in the MS gene.
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/*genetics ; Adult ; Cerebrovascular Accident/*genetics ; DNA/metabolism ; DNA Restriction Enzymes/metabolism ; Family Health ; Female ; Genotype ; Homocysteine/blood/genetics ; *Homozygote ; Human ; Hyperhomocysteinemia/*genetics ; Male ; Polymorphism (Genetics) ; Tetrahydrofolates/*genetics ; Variation (Genetics)

OBJECTIVEThe effect of the gene polymorphism for the key enzyme's folacin metabolism pathway on plasmatic homocysteine (Hcy) levels in fertile woman was observed.

METHODSThe subjects were from Shaoxing City, Jiangsu province in 2012, the selection criteria for the women of childbearing age were between 20-45 years old, with an average age of 28.2 (95%CI:27.8-28.6) years old. Sample collection continued uninterrupted lasted seven days, a total of 535 samples were collected, venous blood with EDTA addition or sodium citrate to anticoagulant. After separation, the blood cells and blood plasma were cryopreserved. DNA was extracted using spin column method. All the samples were selected for the gene polymorphism testing of the key enzyme's on folate metabolism and monitoring of plasmatic Hcy level.

RESULTSEight single nucleotide polymorphism (SNP) sites of methylenetetrahydrofolate reductase gene (MTHFR) , methionine synthase gene (MS) , synthetic methionine reductase gene (MSR) and cystathionine β synthase gene (CBS) were detected. It was found the genotype AA of the SNP sites-rs1801131 would result higher plasmatic Hcy levels (8.99 µmol/L) than the genotypes CC (7.81 µmol/L) and CA(8.38 µmol/L) (P < 0.01) . Similarly, the genotype TT of the SNP sites-rs1801133 was significantly responded to the increasing of Hcy levels (11.10 µmol/L) than the genotype CC (8.15 µmol/L) and CT (8.45 µmol/L), (P < 0.01) . The two sites of genotype combination of AA-TT could also result in the significant increase of Hcy levels (11.02 µmol/L) than other combined genotypes (genotypes CC-CC, CA-CC, CA-CT, AA-CC, AA-CT), especially the genotype CC-CC. And the risk factor was 1.41 (95CI:1.20-1.66) times over the genotype CC-CC.

CONCLUSIONThe gene mutations of two SNP sites rs1801131 and rs1801133 in MTHFR would increase Hcy levels.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Adult ; China ; Cystathionine beta-Synthase ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Folic Acid ; Genotype ; Homocysteine ; blood ; genetics ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; physiology ; Polymorphism, Single Nucleotide ; Risk Factors

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Carrier Proteins ; genetics ; Congenital Abnormalities ; etiology ; Folate Receptors, GPI-Anchored ; Folic Acid Deficiency ; complications ; etiology ; Homocysteine ; blood ; Humans ; Membrane Transport Proteins ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Receptors, Cell Surface ; genetics

OBJECTIVETo investigate the changes of plasma homocysteine (Hcy) level in patients with ischemic cerebrovascular or cardiovascular disease and analyze the relationship between plasma Hcy levels and the mutations in Hcy metabolism related enzymes, including methylene tetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthetase (CBS) 844ins68 and methionine synthetase (MS) A2756G.

METHODSBy using the HPLC-FLD method, the plasma total homocysteine (tHcy) concentration was determined in 86 patients with cerebral infarction, 66 with myocardial infarction and 80 healthy controls. The association of plasma tHcy levels with cardiovascular or cerebrovascular disease and mutations of MTHFR C677T, CBS 844 ins 68 and MS A2756G were evaluated by statistic methods.

RESULTSIn the patient groups, the plasma tHcy concentrations increased significantly as compared with healthy controls. The individuals homozygous for MTHFR C677T mutation had significantly higher plasma Hcy levels.

CONCLUSIONHyperhomocysteinemia is an important risk factor for ischemic cerebrovascular and cardiovascular disease. The homozygosity of MTHFR C677T may contribute to the increase of plasma Hcy and vascular damage.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Brain Ischemia ; blood ; genetics ; Cystathionine beta-Synthase ; genetics ; Female ; Heterozygote ; Homocysteine ; blood ; Homozygote ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Mutation ; Myocardial Ischemia ; blood ; genetics ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Polymorphism, Genetic

BACKGROUNDThe 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are attractive candidates for screening for risk of neural tube defects (NTDs). The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China.

METHODSFifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses.

RESULTSThere was a significant difference for MTHFR genotype distribution for one site (C677T) between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group (55.9% vs. 35.3%, P < 0.05). A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype.

CONCLUSIONGenetic interaction between MTHFR and MS genes raises the probability of neural tube defects.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; China ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Neural Tube Defects ; epidemiology ; genetics ; Polymorphism, Genetic ; genetics