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)

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

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

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: There have been studies on the relations between metabolic syndrome and colorectal cancer or on the relations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and colorectal cancer, but reports on the relationship between metabolic syndrome, MTHFR polymorphism and colorectal cancer all together are rare. The aim of this study is to find the interrelation between metabolic syndrome and MTHFR polymorphism in colorectal cancer. METHODS: This study investigated 255 colorectal cancer patients (cancer group) who underwent surgery in our hospital from March 2003 to December 2008 and compared those patients to 488 healthy patients (control group). The diagnostic criterion for metabolic syndrome was based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), and the MTHFR 677 polymorphism was analyzed. RESULTS: When colorectal cancer patients and patients in the control group were classified as MTHFR 677 subtypes, there was no difference between the two groups: CC 87 (34.1%), CT 134 (52.6%), and TT 34 (13.3%) for the cancer group and CC 145 (32.4%), CT 238 (53.1%), and TT 65 (14.5%) for the control group. Distributions of MTHFR 677C/T genotype and allele frequencies in the individuals with and without metabolic syndrome in the cancer group showed no differences. Moreover, we could find no differences in distributions of MTHFR 677C/T genotypes in the clinical and the biomedical variables of individuals with and without metabolic syndrome in the cancer group. CONCLUSION: Our results show no relation between metabolic syndrome and MTHFR polymorphism in colorectal cancer. However, a further prospective study, based on a precise diagnostic criterion for metabolic syndrome, is needed.
Adenosine Triphosphate ; Cholesterol ; Colorectal Neoplasms ; Gene Frequency ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)