No abstract available.
Humans ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Polymorphism, Genetic*

No abstract available.
Folic Acid* ; Homocysteine* ; Methylenetetrahydrofolate Reductase (NADPH2)*

BACKGROUND: This study was designed to identify the relationship between the C677T mutants of MTHFR and methotrexate toxicities in Korean patients with RA and to determine whether MTHFR polymorphism will be useful predictor for adverse effects of low dose methotrexate treatment. METHODS: We enrolled 385 (355 females, 30 males) patients with RA, who had been received low dose methotrexate. Genotypes of MTHFR polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The correlations between MTHFR genotypes, age, RF positivity, RA progression stage, KHAQ and adverse effects were analyzed by Spearman's rank correlation test. The frequency analysis of C677T genotype and adverse effects was done by Chi-square test. RESULTS: The results of MTHFR genotypic analysis showed 133 patients (34.6%) with 677CC, 193 patients (50.1%) with 677CT and 59 patients (15.3%) with 677TT. One hundred fifty-four of the 385 patients (40.0%) had methotrexate-related side effects. The significant correlation between toxicities of methotrexate and MTHFR polymorphism was identified by Spearman's rank correlation test (p<0.05). The odd ratio, which of adverse effects could be occurred by low dose methotrexate in rheumatoid arthritis patients with MTHFR polymorphism, showed higher value than other studies (p<0.001, OR: 4.0, 95% CI 2.45-6.51). CONCLUSION: There was a positive association between methotrexate-related toxicities and MTHFR polymorphism. This study suggested that C677T mutant of MTHFR might be a powerful genetic indicator in predicting the adverse effects of low dose methotrexate therapy in patient with rheumatoid arthritis.
Arthritis, Rheumatoid* ; Female ; Genotype ; Humans ; Methotrexate* ; Methylenetetrahydrofolate Reductase (NADPH2)*

OBJECTIVE: To analyze the methylenetetrahydrofolate reductase (MTHFR) mutation in patients with recurrent spontaneous abortion. MATERIAL AND METHOD: The blood samples of patients with recurrent spontaneous abortion were tested by PCR-RFLP method. RESULTS: Of 51 cases of study group, 14 (27.5%) were normal, 25 (49.0%) were heterozygosity, and 12 (23.5%) were homozygosity. Of 58 cases of control group, 20 (34.5%) were normal, 30 (51.7%) were heterozygosity, and 8 (13.8%) were homozygosity. But the difference between two groups was not significant (p=0.190). CONCLUSION: Hyperhomocysteinemia due to MTHFR mutation is a cause of recurrent spontaneous abortion. Therefore, the study for MTHFR mutation should be included in the workup of recurrent spontaneous abortion.
Abortion, Spontaneous* ; Female ; Humans ; Hyperhomocysteinemia ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Pregnancy

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)

BACKGROUND: The polymorphisms, C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene express a decreased enzyme activity. These polymorphic variants are known to decrease the risk of some malignancies. We examined whether the polymorphisms in MTHFR gene play a role in childhood acute lymphoblastic leukemia (ALL). METHODS: Peripheral blood or bone marrow samples were collected from 99 ALL patients aged <16 years and 105 age and sex matched controls. We performed PCR-restriction fragment length polymorphism with HinF1 for C677T and MboII A1298C. RESULTS: The frequencies of 677CC, 677CT, and 677TT genotypes were 43.4%, 46.5% and 10.1% in patients and 39.0%, 45.7%, and 15.2% in controls. The 677TT variants seemed to decrease the risk for ALL than the 677CC genotype, but the difference was not statistically significant (OR=0.60, 95% CI=0.2-1.5). The frequencies of 1298AA, 1298AC, and 1298CC genotype were 66.7%, 26.3% and 7.1% in patients and 60.0%, 38.1% and 1.9% in controls. The 1298CC genotype seemed to increase the risk for ALL than 1298AA, but without statistical significance (OR=3.34, 95% CI=0.7- 18.1). These findings were more evident in the patient groups with hyperploid and translocation than those with normal karyotypes. CONCLUSIONS: In our series, MTHFR C677T and A1298C polymorphism did not show a statistically significant protective effect for the childhood ALL.
Bone Marrow ; Genotype ; Humans ; Karyotype ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma*

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for ischemic stroke. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been known to result in reduced MTHFR enzyme activity, and induced hyperhomocysteinemia. Recently, a significant association with ischemic stroke was identified for the homozygous T allele of the MTHFR polymorphism by meta-analysis. This current study was undertaken to determine whether MTHFR C677T polymorphism was associated with ischemic stroke in the Korean population. METHODS: We enrolled 1292 patients with ischemic stroke and 457 healthy individuals and measured their fasting plasma homocysteine levels and analyzed the C677T polymorphisms in the MTHFR gene. RESULTS: The prevalence of the homozygous mutation was significantly higher in ischemic stroke patients (23.9%) than in controls (13.8%; p<0.01). Homocysteine levels in the plasma were significantly higher in ischemic stroke patients (11.76+/-4.94 micro mol/L) than in controls (9.21+/-3.26 micro mol/L: p<0.001). In controls, the homocysteine levels were significantly higher in the TT genotype than in the CC+CT genotypes (adjusted odds ratio (AOR), 1.22; 95%CI, 1.11-1.34). When the homocysteine levels were stratified into high (>or=11.80 micro mol/L), moderate (8.80 to 11.79 micro mol/L), and low (<8.80 micro mol/L) groups, the AOR was significantly greater in subjects with the high group compared with the low group (AOR, 3.61; 95%CI, 2.63 to 4.95). The AOR and 95% confidence intervals was 1.74 (1.27 to 2.37) for the TT genotype in patients with ischemic stroke compared to controls. CONCLUSIONS: We found that the MTHFR C677T polymorphism is an independent risk factor for ischemic stroke in Koreans, and our findings may have the predictive value of ischemic stroke by analyzing genetic defects.
Alleles ; Fasting ; Genotype ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Methylenetetrahydrofolate Reductase (NADPH2) ; Odds Ratio ; Plasma ; Prevalence ; Risk Factors ; Stroke*

PURPOSE: Colon carcinogenesis seems to vary according to the original location of tumor, especially theright and the left sides. Two common methylenetetrahydrofolate reductase (MTHFR) polymorphisms, 677C->T and 1298A->C, are now known. Especially, the TT type of the 677C->T mutation shows reduced catalytic activity at a rate 30% that of wild type. The aim of this study is to investigate the distributions of MTHFR polymorphisms of 677C->T and 1298A->C according to the location of the colon cancer. METHODS: Blood samples were collected from 112 patients diagnosed in our hospital, as having colon cancer: 34 proximal and 78 distal cases to the splenic flexure and 448 healthy control subjects. In order to characterize MTHFR polymorphisms, we applied the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distributions of MTHFR 677C->T polymorphisms as genotypes CC, CT, and TT were 32.4%, 53.1%, and 14.5% in the control group, and 34.8%, 58.0%, and 7.1% in the cancer group (P=0.056). In the 34 proximal cancers, the CC, CT, and TT distributions were 44.1%, 55.9%, and 0% (P<0.05), respectively. In the distal group, they were 30.8%, 59.0%, and 10.3%. The distributions of the MTHFR 1298 A->C polymorphism by genotypes, AA, AC, CC were 69.6%, 28.6%, and 1.8% in the control group, and 58.9%, 38.4%, and 2.7% in the cancer group. The proximal and the distal groups show genotype distributions of 44.1%, 53.0%, and 2.9% and 65.4%, 32.0%, and 2.6%, respectively, but the differences were not statistically significant. CONCLUSIONS: There are no definite differences between control subjects and colon-cancer patients in the two polymorphisms 677C->T and 1298A->C. However, the TT genotype shows a lower frequency in the cancer group than in the control group with a marginal statistical value (P=0.056), which suggest a reduced risk of cancer incidence for this type, compared with a CC or a CT type.
Carcinogenesis ; Colon* ; Colon, Transverse ; Colonic Neoplasms* ; Genotype ; Humans ; Incidence ; Methylenetetrahydrofolate Reductase (NADPH2)

Unexplained male infertility is mostly due to sperm-related gene mutations in the spermatogenic process. Methylenetetrahydrofolate reductase (MTHFR) plays an important role in the process of DNA, RNA and protein metabolism, and is closely related with spermatogenesis. Researchers have found more than 20 single nucleotide polymorphisms (SNP) of the MTHFR gene. The polymorphisms of MTHFRC677T and A1298C may have a close relationship with male infertility. But the correlation between MTHFRG1793 and male infertility needs to be further studied.
Humans ; Infertility, Male ; genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo construct a small interfering RNA (siRNA) eukaryotic expression vector specific for methylene tetrahydrofolate reductase (MTHFR) gene and to observe its silencing effect on MTHFR gene.

METHODSThe expression vectors of PsiRNA-MTHFR were constructed by gene recombination and then were nucleofected into the primary cultured MEPM cell. At 48 h and 5 d after nucleofection, the expression of MTHFR in the levels of mRNA and protein was detected by real-time quantitative polymerase chain reaction (Real-Time PCR) and Western blot.

RESULTSThe eukaryotic expression vector of PsiRNA-MTHFR, which significantly down-regulated mRNA and protein of MTHFR at 48 h and 5 d after nucleofection, were successfully constructed.

CONCLUSIONEukaryotic expression vector of siRNA specific for MTHFR is successfully contructed, which lays the basis for its application in the mechanism research of MTHFR gene regulating embryo palate shelves fusion.