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

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

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)

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)

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*

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*

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)*

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