A Wiki about biochemical individuality


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  • Official Symbol: MTHFR
  • Name: 5,10-methylenetetrahydrofolate reductase (NADPH)
  • Gene type: protein coding
  • Gene name: MTHFR
  • Gene description: 5,10-methylenetetrahydrofolate reductase (NADPH)
  • Chromosome: 1; Location: 1p36.3
  • Organism: Homo sapiens

Methylenetetrahydrofolate reductase (EC catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.

Literature Review

Cardiovascular disease
  • C677T MTHFR mutation is strongly associated with arterial stroke especially in young adults.  PubMed
  • Methylenetetrahydrofolate reductase gene polymorphism is associated with endothelial dysfunction in healthy young men.  PubMed
  • Association between hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of myocardial infarct  PubMed
  • The prevalence of homozygous gene mutation for MTHFR was higher among patients with stroke than control subjects  PubMed
  • Greater risk of abdominal aortic aneurysm in carriers of the MTHFR 677T allele  PubMed
  • The interaction between MTHFR 677 C-->T genotype and folate status is a determinant of coronary atherosclerosis risk.  PubMed
  • The MTHFR TT genotype is a risk factor for hypertension and carotid stenosis in Japanese women. Significant interactions with smoking were observed in women but not in men. Smoking cessation is important for prevention of cerebrovascular disease  PubMed
  • MTHFR polymorphism can be a genetic risk factor developing coronary diseases in the third world countries where folate deficiency is quite common.  PubMed
  • Homozygosity for the C677T mutation in the MTHFR gene does not constitute a genetic risk factor for coronary diseases and neural tube defects in the Indonesian Javanese population.  PubMed
  • Severity of CAD and is related to the MTHFR polymorphism, suggesting an interesting link between coronary atherosclerosis and genetic instability in humans.  PubMed
Drug interactions
  • Results suggest that the genotyping for thymidylate synthase and methylenetetrahydrofolate reductase polymorphisms may be a useful indicator in determining the appropriate dose of methotrexate in patients with rheumatoid arthritis.  PubMed
  • MTHFR C677T polymorhism may indicate the need to reduce the dose of methotrexate during prolonged administration to prevent toxicity.  PubMed
  • MTHFR polymorphism is associated with tumor response to fluoropyrimidine-based chemotherapy for advanced colorectal neoplasms  PubMed
  • Polymorphisms in MTHFR is associated with the efficacy and toxicity of methotrexate used for the treatment of rhematoid arthritis  PubMed
  • Deficient MTHFR function due to loss of an MTHFR allele by an evolving neoplasm might, by promoting chromosomal losses, accelerate cancer development  PubMed
  • Homozygosity for the low-activity C677T genotype (TT) of MTHFR may represent a genetic determinant increasing breast cancer risk  PubMed
  • Hypomethylation and Methylenetetrahydrofolate reductase gene polymorphism is associated with gastric cancer  PubMed
  • Individuals with the variant alleles MTHFR 677T had a decreased risk of colorectal adenoma, suggesting that folate inhibits the growth of colorectal adenomas,  PubMed
  • MTHFR C677T polymorphisms may affect long-term survival from advanced breast cancer  PubMed
  • Methylenetetrahydrofolate reductase may have a role in relapse and progression of chronic myelogenous leukemia  PubMed
  • Polymorphismsof methylenetetrahydrofolate reductase are associated with chronic lymphocytic leukemia  PubMed
  • The MTHFR gene polymorphism maybe associated with reduced risk of progression of prostate cancer.  PubMed
  • Polymorphisms of methylenetetrahydrofolate reductase (NADPH) is associated wtih bladder cancer  PubMed
  • Finds no association between MTHFR 677 C->T or 1298 A->C polymorphisms and endometrial cancer risk.  PubMed
  • Polymorphisms in the MTHFR gene are associated with breast cancer in premenopausal women.  PubMed
  • The exclusive pattern of MTHFR allele loss in cases of LOH, suggest that functional MTHFR activity within a tumor might play an important role in the survival and progression of a colonic neoplasm.  PubMed
  • There are associations between the genotypes of this enzyme and the risk of developing acute leukemia.  PubMed
  • The polymorphisms of MTHFR C677T was associated with risk of developing stomach cancer.  PubMed
  • MTHFR polymorphism is associated with marked mtx-induced hyperhomocysteinemia in ovarian cancer  PubMed
  • Polymorphism in Mthfr gene is associated with colorectal cancer risk  PubMed
  • The risk of developing gastric cancer in the individuals with MTHFRC677T/C1298C was 17 times higher than that in the individuals with MTHFRC677C/A1298A.  PubMed
  • MTHFR may be required for tumor survival. Antisense inhibition of MTHFR reduces survival of methionine-dependent tumor cell lines.  PubMed
Birth Defects
  • Embryos with combined MTHFR 677TT and TC 776CG or 776GG genotypes; genotypes individually associated with impaired homocysteine metabolism in adults, are at increased risk for spontaneous abortion compared with embryos with only one of these genotypes.  PubMed
  • Absence of association of fetal MTHFR C677T polymorphism with prenatal Down syndrome pregnancies  PubMed
  • These findings suggest a possible role of MTHFR and folic acid in the causation of orofacial clefts, but the strength and direction of these effects remain to be clarified.  PubMed
  • Maternal 677CT/1298AC genotype as a risk factor for cleft lip  PubMed
  • An allele of this enzyme is prefertially transmitted to infants with Down syndrome: implications for a survival advantage  PubMed
  • Methylenetetrahydrofolate reductase polymorphism in the etiology of Down Syndrome.  PubMed
  • Mutants may be associated with neural tube defects, but associated is too weak to recommend using MTHFR for screening.  PubMed
  • Prevalence of FVL, FII G20210A and MTHFR C677T in women with three or more pregnancy losses  PubMed
  • High prevalence of mutated MTHFR genotypes in spontaneously aborted embryos  PubMed
  • The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene results in reduced MTHFR enzyme activity and reduced methylation of homocysteine to methionine resulting in mild hyperhomocysteinaemia  PubMed
  • Although generally reduced in the younger age groups, the homocysteine plasma levels were shown to increase in individuals according to the number of mutations, especially those of the 677T allele.  PubMed
  • Hyperhomocysteinemia, serum folate levels and both C677T and A1298C MTHFR mutations are associated with cardiovascular disease in hemodialysis patients.  PubMed
  • The mutation of MTHFR gene can be modified by dietary supplement of vitamin B12 as well as folate to reduce homocysteine levels of atherosclerotic patients.  PubMed
  • The polymorphisms C677T and A1298C of MTHFR and fasting plasma homocysteine levels do not seem to be significant risk factors for venous thromboembolic disease.  PubMed
  • The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants.  PubMed
  • Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms.  PubMed
  • TYMS and MTHFR compete for limiting supplies of folate required for the remethylation of homocysteine.  PubMed
  • Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage.  PubMed
  • Hyperhomocysteinemia and the homozygous C677T mutation in the MTHFR gene are important risk factors of Budd Chiari syndrome.  PubMed
  • Methylenetetrahydrofolate reductase TT genotype homozygotes require higher folate intakes to achieve similar homocysteine concentrations  PubMed
Other Associations
  • Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: association is significant in men but not in women.  PubMed
  • In MTHFR C677T carriers, acetylcholinesterase activity was significantly higher  PubMed
  • MTHFR gene polymorphisms is associated with sudden hearing loss  PubMed
  • A minor role for polymorphism of this enzyme in the pathogenesis of schizophrenia and depression cannnot be ruled out and would warrant further investigation.  PubMed
  • Risk of migraineurs with aura is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.  PubMed
  • Subjects with the MTHFR 677TT genotype tended to perform better on cognitive tasks than CC/CT subjects.  PubMed
  • A genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in chronic hepatitis C  PubMed
  • Determination of MTHFR polymorphisms and CAG repeat lengths enables screening for subjects with putative early Huntington's disease onset.  PubMed
  • The 677C-->T mutation of MTHFR was present in 26.1% of adults with idiopathic osteonecrosis of the femur head and appears to have a role in the complex pathophysiology of the disease.  PubMed
  • 1The common methylenetetrahydrofolate reductase C677-->T gene polymorphism was investigated as a risk factor for Alzheimer's disease. The MTHFR C677-->T and polymorphism did not appear to confer an added risk for AD.  PubMed
  • C677T polymorphism is a risk factor for diabetic nephropathy in male patients with type 2 diabetes, and that the CT + TT genotype increases in frequency with each stage of diabetic nephropathy.  PubMed
  • This study evidence of an allelic association between METHFR and schizophreia.the T667T, C1298C,C677T/C1298C and T677T/A1298A feneotypes were more frequently recorded among schizophrenic patients.  PubMed
  • A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.  PubMed