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

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

OBJECTIVETo investigate polymorphisms of homocysteine metabolism enzyme-related genes methionine synthase (MS) and methionine synthase reductase (MSR) in Buyi, Dong, Miao ethnics from Guizhou.

METHODSGenotypes of MS and MSR genes of healthy individuals from the three ethnic groups were determined with a TaqMan-MGB probe genotyping method and compared.

RESULTSFor Buyi, Dong and Miao ethnics from Guizhou, frequencies of MS gene 2756G allele were respectively 12.0%, 8.9% and 15.4%. However, no significant difference was found by statistics. Frequencies of MS A2756G alleles for the three ethnic groups are similar to those of Han Chinese from Beijing and Henan, Hui ethnics from Ningxia as well as European populations, but differ significantly from those of Japanese, Indians, Africans and Nigerians (P < 0.05). Frequencies of MSR gene 66 G allele were respectively 32.3%, 30.4% and 21.2% for Buyi, Dong and Miao ethnics. Miao is significantly lower than Buyi and Dong (P< 0.05). Frequencies of MSR gene A66G alleles for the three ethnic groups are similar to those of Han Chinese from Beijing and Guangdong, Japanese, Africans and Nigerians populations, but differ significantly from those of Indians and European (P< 0.05).

CONCLUSIONThe distributions of MS gene A2756G and MSR gene A66G polymorphisms have differed significantly between the three ethnic groups and individuals from various regions.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Ethnic Groups ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

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 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

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

OBJECTIVETo examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase (MTHFR) gene and methionine synthase (MS) gene.

METHODSA total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine (tHcy) concentration was measured by high-performance liquid chromatography (HPLC). Lipid profiles were measured for all subjects. The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP.

RESULTSThe tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control (15.95 micromol/L vs 13.43 micromol/L, P < 0.05). The prevalence of hyperhomocysteinemia (HHcy) in the combined hyperlipidemia group was significantly higher than that in the control (42.2% vs. 23.0%, P = 0.015), with the odds ratio (OR) of 3.339 (95% CI: 1.260-8.849). The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol (TC) than that in the normal tHcy patients (5.67 +/- 0.95 mmol/L vs. 5.47 +/- 0.92 mmol/L, P=0.034). There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride (TG) than those with CC genotype (2.24 +/- 1.75 mmol/L vs 1.87 +/- 0.95 mmol/L, P < 0.05). Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group (12.61 +/- 1.24 micromol/L vs. 11.20 +/- 1.37 micromol/L, P < 0.05) and in the control group (14.04 +/- 1.48 micromol/L vs. 12.61 +/- 1.24 micromol/L, P < 0.05). The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control (26.7% vs. 13.0%, P = 0.012), with the OR of 3.121 (95% CI: 1.288-7.651). The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC (5.87 +/- 0.89 mmol/L vs. 5.46 +/- 0.93 mmol/L, P < 0.05) and LDL-C (3.29 +/- 0.81 mmol/L vs. 2.94 +/- 0.85 mmol/L, P < 0.05) than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype.

CONCLUSIONHHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Female ; Genotype ; Homocysteine ; blood ; metabolism ; Humans ; Hyperhomocysteinemia ; blood ; genetics ; pathology ; Hyperlipidemias ; blood ; genetics ; pathology ; Lipids ; blood ; genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic ; Risk Factors

OBJECTIVETo explore the significance of gene mutation of methylenetetrahydrofolate reductase (MTHFR) C677T, methionine synthase (MS) 2756 AG and cystathionine beta-synthase (CBS) 844ins68 in the development of deep venous thrombosis.

METHODSOne hundred and three cases of deep venous thrombosis (DVT group) and 250 healthy subjects (control group) were recruited in the study. The polymorphisms of MTHFR C677T, MS A2756G and CBS 844ins68 were detected by PCR-restriction fragment length polymorphism(PCR-RFLP).

RESULTSThe prevalences of TT genotypes of MTHFR (C677T) between DVT group and normal control group had significant difference (27.2% vs 17.2%, P< 0.05), the prevalence of AG genotypes of MS A2756G in the DVT group was less than that in the control group (9.7% vs 19.2%, P< 0.05). The prevalence of 677T-2756A haplotype in the DVT group was higher than that in the control group (P< 0.05), the prevalence of 677C-2756A haplotype in the DVT group was less than that in the control group (P< 0.05). There were no significant differences in the prevalences of CBS 844ins68 mutation.

CONCLUSIONThe homozygote of MTHFR C677T (TT) may be a risk factor of DVT. MS A2756 G(AG) genotypes may reduce the development of DVT. The 677T-2756A haplotype may be a risk factor of DVT. The 677C-2756A haplotype may be a protective factor of DVT. The prevalence of gene mutation of CBS 844ins68 might vary with different ethnic group or geographic regions.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Adult ; Alleles ; Cystathionine beta-Synthase ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Point Mutation ; Polymorphism, Genetic ; Venous Thrombosis ; enzymology ; genetics

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 interrelationship of genetic polymorphisms in folate metabolic enzymes (MTHFRC677T, MTHFRA1298C, MTRA2756G and MTRRA66G) and their combinative effects with colorectal cancer (CRC).

METHODSA nested case-control study was designed and carried out. 140 CRC patients and 343 control subjects were included in this study. Polymorphisms of folate metabolic enzyme genes were genotyped by PCR-restriction fragment length polymorphism method. Risk of CRC was estimated by unconditional logistic model, and P value for interaction was calculated by likelihood test.

RESULTSThe allele of MTR2756G showed a positive association with CRC (OR = 2.04, 95% CI = 1.22 - 3.40). Those with MTHFR1298AA and MTR 2756AG/GG genotypes had an elevated risk with CRC (OR = 2.57, 95% CI, 1.42 -4.65), and their combinative effect showed a significant association with CRC (P = 0.04).

CONCLUSIONMTR2756G allele may be a risk factor of CRC, and interaction may exsit between polymorphisms of MTHFRA1298C and MTRA2756G. Further studies with larger sample and in different ethnic groups are needed.

5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase ; genetics ; Alleles ; Case-Control Studies ; Colorectal Neoplasms ; enzymology ; genetics ; Female ; Ferredoxin-NADP Reductase ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length