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*

Hyperuricemia is related to metabolic syndrome, and is defined as an over-production or under-excretion of uric acid (UA), with increased UA serum concentration. Among other causes, Hyper-homocysteinemia (H-Hcy) can be responsible for hyperuricemia. The mechanisms underlying the association between these two conditions are unclear, but increased UA serum levels can be a consequence of renovascular atherosclerosis, with reduced UA excretion. An alternative hypothesis is the over-production of UA from adenosine (originating from S-adenosyl-homocysteine). Genetic polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) may contribute. A possible mechanism is purines biosyinthesis originating from this gene variant. However, the results obtained from several studies and meta-analyses of the relationship between H-Hcy and hyperuricemia are ambivalent, and broader research is needed.
Adenosine ; Atherosclerosis ; Homocysteine ; Hyperuricemia* ; Methylenetetrahydrofolate Reductase (NADPH2) ; Polymorphism, Genetic ; Purines ; Uric Acid

PURPOSE: The C677T polymorphism of the methylenetetrahydrofolate reductase(MTHFR) has been suggested as a risk factor of maternal meiotic nondisjunction for Down syndrome. Recently, a second genetic polymorphism in MTHFR at position 1298 was reported. However, a positive association between the A1298C MTHFR polymorphism and Down syndrome has not been reported. Therefore, this study was undertaken to determine which polymorphism of MTHFR gene was associated with the increased risk of a child suffering from Down syndrome(DS). METHODS: We enrolled 33 patients with Down syndrome and 100 healthy individuals and analyzed the MTHFR C677T and A1298C polymorphism by a PCR-restriction fragment length assay. RESULTS: Frequencies of MTHFR C677T genotypes(CC, CT, and TT) were 9(27%), 22(67%), and 2 (6%) in the DS patients and 24(24%), 55(55%) and 21(21%) in the control, respectively. The frequency of mutant 677TT was significantly low in the DS patients(OR : 0.14; 95% CI : 0.02-0.95; P= 0.04). For the MTHFR A1298C polymorphism, frequencies of genotypes(AA, AC, and CC) were 16(48 %), 15(45%) and 1(3%) in DS patients and 77(77%), 21(21%) and 2(2%) in the control, respectively. The frequency of mutant 1298AC was significantly increased in DS patients with an odds ratio of 3.3(95% CI : 1.39-7.82; P=0.007). CONCLUSION: Our results suggest that MTHFR mutant 677TT may have a protective effect against Down syndrome, but MTHFR mutant 1298AC may be an independent risk factor in Down syndrome.
Child ; Down Syndrome* ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Odds Ratio ; Polymorphism, Genetic ; Risk Factors

BACKGROUND: Folic acid has been frequently used for hyperhomocyesteinemia in various diseases and decreases the level of homocysteine. OBJECTIVES: To assess the effect of folic acid in the level of homocysteine in epilepsy patients, and to analyze factors affecting its responsiveness and the difference of its efficacy according to methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. METHODS: Total 75 epilepsy patients with antiepileptic drugs (AEDs) therapy were included. 41 patients had normal level of homocysteine and 34 patients with hyperhomocysteinemia (> or =12 micro mol/ ) were supplemented with folic acid for 1 year. Thirty-four patients with hyperhomocyteinemia were divided into two groups according to the responsiveness of homocysteine to folic acid; decrease group (DG) and non-decrease group (NDG). RESULTS: The level of homocysteine in patients with hyperhomocysteinemia was significantly decreased after administration of folic acid, comparing with patients with normal level. DG was younger and had more male gender, shorter duration of seizure, and initial higher homocysteine level, compared to NDG (p<0.05). Patients with mutant type of MTHFR (CT+TT) had more decreased homocysteine level after supplement of folic acid, but had more increased homocysteine level without supplement of folic acid. Comparing between MTHFR genotypes, TT type had the most decreased homocysteine level than others, but there was no significance. CONCLUSION: Folic acid is useful treatment of hyperhomocysteinemia in epilepsy patients and the supplement of folic acid might be considered in patients with mutant type of MTHFR regardless of homocysteine level. The effect of folic acid supplement is greater in younger age, male sex, shorter duration of seizure, and initial higher homocysteine level.
Anticonvulsants ; Epilepsy* ; Folic Acid* ; Genotype ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Seizures

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) deficiency is rare in severe cases but common in mild cases. TT genotype of C677T of MTHFR shows reduced enzyme activity and hyperhomocysteinemia. It has been shown that homocysteine is very toxic to dopaminergic neuronal cell in vitro and animal experiment, which suggests some role of homocysteine in the pathogenesis of Parkinson's disease (PD). This study examined the association of MTHFR genotype, hyperhomocysteinemia, and Parkinson's disease. METHODS: Serum homocysteine concentration and the C677T genotypes of MTHFR were assessed in 80 patients with Parkinson's disease, and 80 healthy subjects matched for age and gender, in a hospital-based setting. RESULTS: Proportion of moderate hyperhomocysteinemia (plasma homocyst(e)ine > or =15 micromol/L) was higher in patients with Parkinson's disease than in normal controls (53.7% vs 30.0%, p=0.01). TT genotype of MTHFR was highly frequent in Parkinson's disease patients compared to controls (18.7% vs 11.3%, p=0.01). The combination of hyperhomocysteinemia and TT genotype of MTHFR augmented risk for Parkinson's disease (odds ratio 2.53 [95% confidence interval, 1.48-4.31, p=0.01]). CONCLUSIONS: Hyperhomocysteinemia is a common finding in the patients with Parkinson's disease. TT genotype of MTHFR is at increased risk for Parkinson's disease, and in conjunction with hyperhomocyeteinemia, augments the association.
Animal Experimentation ; Dopaminergic Neurons ; Genotype* ; Homocysteine ; Humans ; Hyperhomocysteinemia* ; Methylenetetrahydrofolate Reductase (NADPH2) ; Parkinson Disease*