Correlation between methylenetetrahydrofolate reductase gene C677T polymorphism and plasma homocysteine levels and white matte hyperintensities: a meta-analysis / 国际脑血管病杂志

Objective To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and plasma homocysteine (Hcy) levels and white matte hyperintensities (WMHs). Methods PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Weipu and Wanfang databases were retrieved to search studies on correlation between MTHFR gene C677T polymorphism and plasma Hcy levels and WMHs. The search deadline was October 31, 2018. Stata 14.0 software was used for statistical analysis. Results Six eligible literatures on the correlation between MTHFR gene and WMHs were included. The results of meta-analysis showed that there was no significant correlation between MTHFR C677T gene polymorphism and WMHs in 5 genetic models (T allele vs. C allele, TC vs. CC genotype, TT vs. CC genotype, TT+TC vs. CC genotype, and TT vs. TC+CC genotype). A total of 22 eligible literatures on the correlation between plasma Hcy level and WMHs were included. The results of meta-analysis showed that the plasma Hcy levels in patients with WMHs were significantly higher than those in the control group (weighted mean difference 3.48, 95% confidence interval 2.36-4.60; Z=6.03, P<0.01). Conclusions There was no significant correlation between MTHFR gene C677T polymorphism and WMHs, and the elevated plasma Hcy levels may be a risk factor for WMHs.

Association between folate metabolism-related genes and non-syndromic cleft lip and palate in the popu-lation of Shanxi Province / 实用口腔医学杂志

Objective:To investigate the association of the rsl801133 polymorphisms of the methylenetetrahydrofolate reductase (MTHFR)gene and rs2236225 polymorphisms of the methylenetetrahydrofolate dehydrogenase(MTHFD1)gene with non-syndromic cleft lip with or without cleft palate (NSCL/P)in Chinese population of Shanxi Province.Methods:The rsl801133 polymorphism of MTHFR gene and rs2236225 polymorphism of MTHFD1 gene were examined by PCR-RFLP in 265 patients with NSCL/P and 276 healthy controls.Data were statistically analysed.Results:The genotypic distribution of rsl801133 and rs2236225 was not deviated from the Hardy-Weinberg equilibrium.There was no significant difference in allele frequencies of rsl801133 and rs2236225 variants between patients with NSCL/P and healthy individuals(P <0.05).Conclusion:The polymorphism of MTHFR gene and MTHFD1 gene was not associated with NSCL/P in Chinese population of Shanxi Province.

MTHFR C677T Polymorphism as a Risk Factor for Vascular Calcification in Chronic Hemodialysis Patients

Polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T is one of the suggested risk factors for atherosclerosis. However, few studies have reported on the relationship between MTHFR C677T polymorphism and vascular calcification (VC) in chronic hemodialysis patients. We investigated the relationship between the MTHFR C677T polymorphism and VC in 152 chronic hemodialysis patients. Patients with a TT genotype exhibited significantly higher VC scores than patients expressing CC and CT (P = 0.002). The prevalence of peripheral vascular disease increased with the incidence of MTHFR C677T mutations for all patients, and the incidence of cerebrovascular accidents also increased with the presence of mutations for young patients (< or = 60 yr) (P < 0.05). Patients with CT and TT genotypes had adjusted odds ratios for VC of 1.39 and 1.58, respectively (P < 0.05). In summary, these data suggest that the MTHFR C677T polymorphism affects the degree of VC in chronic hemodialysis patients.

Homocistéina e metilenotetrahidrofolato redutase em indivíduos submetidos à angiografia coronariana / Homocysteine and methylenetetrahydrofolate reductase in subjects undergoing coronary angiography

OBJETIVO: Determinar os níveis plasmáticos de homocisteína e a incidência do polimorfismo C677T no gene da enzima metilenotetrahidrofolato redutase (MTHFR) em um grupo de indivíduos submetidos a angiografia coronariana, buscando estabelecer a possível correlação entre esses parâmetros e a gravidade da doença arterial coronariana (DAC), bem como investigar a correlação entre hiper-homocisteinemia e a presença do polimorfismo. MÉTODOS: Vinte indivíduos com ausência de ateromatose nas coronárias (controles), quatorze indivíduos apresentando ateromatose leve/moderada e vinte e nove indivíduos apresentando ateromatose grave foram avaliados. RESULTADOS: Para o parâmetro homocisteína foram observadas diferenças significativas entre as médias dos grupos controle e ateromatose grave (p < 0,001). Entre os demais grupos não foram observadas diferenças significativas. O grupo ateromatose grave apresentou uma freqüência de 62,0 por cento e 6,9 por cento para o polimorfismo C677T no gene da enzima MTHFR, em heterozigose e homozigose, respectivamente. Entretanto, não foi observada correlação entre a presença da mutação e hiper-homocisteinemia. Foi observada uma correlação positiva da ordem de 41,91 por cento (p < 0,001) entre hiper-homocisteinemia e a presença de DAC. CONCLUSÃO: O achado mais importante deste estudo foi a associação entre hiper-homocisteinemia e a presença de estenose coronariana superior a 70 por cento; entretanto, permanece a dúvida se o aumento da concentração plasmática de homocisteína constitui um fator determinante para o agravamento da lesão aterosclerótica nas coronárias ou se o mesmo é uma conseqüência desta lesão.

OBJECTIVE: To determine plasma homocysteine levels and the incidence of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD), as well as investigate the correlation between hyperhomocysteinemia and the presence of polymorphism. METHODS: Twenty subjects with no coronary atheromatosis (controls), fourteen subjects with mild/moderate atheromatosis, and twenty-nine subjects with severe atheromatosis were evaluated. RESULTS: Significant differences were observed in mean homocysteine levels between the control and the severe atheromatosis groups (p < 0.001). No significant differences were observed among the other groups. The severe atheromatosis group showed rates of 62.0 percent and 6.9 percent for the C677T MTHFR gene polymorphism, in heterozygous and homozygous subjects, respectively. However, there was no correlation between the presence of mutation and hyperhomocysteinemia. A positive correlation of 41.91 percent (p < 0.001) was found between hyperhomocysteinemia and CAD. CONCLUSION: The most important finding of this study was the association between hyperhomocysteinemia and coronary stenosis > 70 percent; yet, whether elevated plasma homocysteine worsens atherosclerosis or is a consequence remains to be established.

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

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.

The Relationship of Methylenetetrahydrofolate Reductase(MTHFR) C677T, Thymidylate Synthase(TS) Gene Polymorphism and Epilepsy / 대한간질학회지

PURPOSE: Thymidylate synthase (TS) gene encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a tandem repeat polymorphism, of which a triple repeat is associated with increased expression of TS. TS is a key enzyme in the folate metabolism and compete with methylenetetrahydrofolate reductase (MTHFR) for limiting supplies of folate required for the remethylation of homocysteine. We studied to clarify the association between MTHFR C677T and TS polymorphism and prognosis in epilepsy. METHODS: 119 patients with antiepileptic drug more than one year were included. We investigated the MTHFR C677T and TS polymorphism using PCR, and analyzed the association between plasma homocysteine, folate levels, clinical profiles (especially seizure frequencies) and polymorphism. RESULTS: In seizure frequencies during one year, TT type in MTHFR and 3R3R type in TS polymorphism had higher frequencies than any other types without statistical significance. In plasma homocysteine levels, TT type had significantly higher homocsyteine levels than any other types, but 3R3R type had higher homocsyteine levels than any other types without statistical significance. Combined analysis of MTHFR C677T and TS polymorphism revealed that plasma homocysteine levels (18.22+/-8.32 micromol/l; p=0.039) and seizure frequencies (6.38+/-7.35/year; p=0.04) in patients with TT/3R3R were significantly higher than any other groups. A significant correlation between plasma homocysteine levels and seizure frequencies also was shown in multivariate linear regression analysis (B=0.160, Std error=0.069, adjusted R2=0.039, p=0.021). CONCLUSION: Epileptic patients with hyperhomocysteinemia, especially when combined with mutant allele for MTHFR and TS genes, have higher seizure frequencies. Therefore, our results suggest that the genotyping for the MTHFR and TS polymorphism may become a useful indicator in determining prognosis of epilepsy.