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

No abstract available.
Folic Acid* ; Homocysteine* ; 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: 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)*

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)

We present a case of suprarenal & infrarenal absence of inferior vena cava combined with hyperhomocysteinemia in a 39-year-old woman who presented with symptoms of deep venous thrombosis. The patient has also C677T methylenetetrahydrofolate reductase homozygous mutation. Deep vein thrombosis has multifactorial etiology involving both genetic and acquired factors. Absence of inferior vena cava is a rare congenital anomaly, but recently it was confirmed as important risk factor for the development of deep vein thrombosis especially young person. Hypercoagulability by the hyperhomocysteinemia with suggested tendency to venous stasis mediated by agenesis of inferior vena cava must have caused the deep vein thrombosis in our patient. To our knowledge, such an association has not been reported. Clinical features and prognosis of this entity are discussed.
Adult ; Female ; Humans ; Hyperhomocysteinemia* ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Prognosis ; Risk Factors ; Thrombophilia ; Vena Cava, Inferior* ; Venous Thrombosis*

OBJECTIVE: This study was performed to understand the influence of the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) genotypes on the spontaneously aborted embryos. METHODS: DNA was extracted from tissue samples of 95 spontaneously aborted embryos and 100 samples of normal children randomly and 449 samples of normal adults were selected as the controls. MTHFR genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The aborted embryo group had higher frequency of MTHFR 677CC type (p=0.014) and lower 677CT type (p=0.063) than the controlled child group. The frequency of MTHFR 677CT type was drastically lower than that of controlled adult group (p=0.032). In the MTHFR C677T/A1298C combination, 677CC/1298AC genotype of the aborted embryo was significantly higher (p=0.034) than that of controlled child group, but it was not statistically significant in controlled adult group (p=0.063). CONCLUSION: MTHFR 677CC and MTHFR 677CC/1298AC genotypes may represent genetic markers for the risk of spontaneously aborted embryos at least in Koreans.
Aborted Fetus* ; Adult ; Child ; DNA ; Genetic Markers ; Genotype ; Homocysteine ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)*

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascualr disease. Recently, a mutation (677C-->T) was identified in the methylenetetrahydrofolate reductase gene leading to the substitution of valine(V) for alanine(A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gen and serum total homocysteine and folate concentrations in Korean healthy subjects. METHODS: In 198 healthy subjects, the methylenetetrahydrofolate reductase genotypes were analyzed by polymerase chain reaction followed by HinfI digestion. Serum total homocysteine and folate concentrations were measured in age- and sex-matched 14 healthy subjects in each of three methylenetetrahydrofolate reductase genotypes. RESULTS: Homozygosity for 677C-->T mutation in the methylenetetrahydrofolate reductase gene was found in 31 (15.7%) of 198 healthy subjects. In healthy subjects, those bearing the VV genotype tend to have higher serum total homocysteine concentrations 1.5 micromol/L(18.6%) than AA genotype but this was not statistically significant. Correlation between serum total homocysteine concentrations and other clinical variables showed that serum folate and creatinine were significant. CONCLUSION: We conclude that although the frequency of VV genotype in Korean healthy subjects is higher than that of other reports, this mutation is not associated with increased serum total homocysteine concentrations in Korean healthy subjects.
Alleles ; Creatinine ; Digestion ; Folic Acid* ; Genotype ; Homocysteine* ; Hyperhomocysteinemia ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Polymerase Chain Reaction ; Risk Factors

OBJECTIVE : To analyze the methylenetetrahydrofolate reductase (MTHFR) mutation in recurrent spontaneous abortion associated with hyperhomocysteinemia. MATERIAL AND METHOD: The blood Sample of habitual aborter with high fasting homocysteine level was tested by PCR-RFLP method. RESULTS: The patient was found to be a homozygosity for MTHFR gene mutation that was confirmed by the finding which is consistent with the mutation at the nucleotide 677 C to T, Corresponding to Ala to Val. CONCLUSIONS: Hyperhomocysteinemia due to MTHFR mutation is a cause of recurrent spontaneous abortion. Therefore, the MTHFR mutation should be examined in the workup of recurrent spontaneous abortion showing hyperhomocysteinemia.
Abortion, Spontaneous* ; Fasting ; Female ; Homocysteine ; Humans ; Hyperhomocysteinemia* ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Pregnancy

OBJECTIVE: To analyze the interrelationship between homocysteine and methylenetetrahydrofolate reductase (MTHFR) mutation in patients with recurrent spontaneous abortion. MATERIAL AND METHOD: Homocysteine and MTHFR mutation were tested by fluorescent polarizing immunoassay and PCR-RFLP method, respectively. RESULTS: In patients with homocysteine level less than 5 mmol/L, there was no case of normal group but there were four cases of heterozygosity and one case of homozygosity. In patients with homocysteine level 5~10 mmol/L, the number of normal, heterozygosity and homozygosity group were eleven, eighteen and eight, respectively. In patients with homocysteine level 10~15 mmol/L, the number of normal, heterozygosity and homozygosity group were four, one and one, respectively. In patients with homocysteine level more than 15 mmol/L, there was no case of normal and heterozygosity group but there were two cases of homozygosity. CONCLUSIONS: Hyperhomocysteinemia due to MTHFR mutation is a cause of recurrent spontaneous abortion. And there was a significant relationship between homocysteine and MTHFR mutation.
Abortion, Spontaneous* ; Female ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Immunoassay ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Pregnancy