Methylenetetrahydrofolate gene

Bagley PJ, Selhub J. A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells. Proc Natl Acad Sci USA 1998 95 13217-13220. 

Brattstrom L, Zhang Y, Hurtig M et al. A common methylenetetrahydrofolate reductase gene mutation and longevity. Atherosclerosis 1998 141 315-319. 

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH2-THF) to 5-methyltetrahydrofolate (CH3-THF). CH3-THF then serves as a methyl donor for the synthesis of methionine. The MTHFR proteins and genes from mammalian liver and E. coli have been characterized,12"15 and MTHFR genes have been identified in S. cerevisiae16 and other organisms. The MTHFR of E. coli (MetF) is a homotetramer of 33-kDa subunits that prefers NADH as reductant,12 whereas mammalian MTHFRs are homodimers of 77-kDa subunits that prefer NADPH and are allosterically inhibited by AdoMet.13,14 Mammalian MTHFRs have a two-domain structure the amino-terminal domain shows 30% sequence identity to E. coli MetF, and is catalytic the carboxyterminal domain has been implicated in AdoMet-mediated inhibition of enzyme activity.13,14... 

GOYETTE, P., PAI, A., MILOS, R., FROSST, P., TRAN, P., CHEN, Z., CHAN, M.,.ROZEN, R., Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR), Mamm. Genome, 1998,9,652-656. 

RAYMOND, R.K., KASTANOS, E.K., APPLING, D.R., Saccharomyces cerevisiae expresses two genes encoding isozymes of methylenetetrahydrofolate reductase, Arch. Biochem. Biophys., 1999,372, 300-308. 

Urano, W., Taniguchi, A., Yamanaka, H., et al. (2002) Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics. 12, 183-190. 

Kumagai, K., Hiyama, K., Oyama, T., Maeda, H., and Kohno, N. (2003) Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. International Journal of Molecular Medicine. 11, 593-600. 

Jakobsen A, Nielsen JN, Gyldenkerne N et al. Thymidylate synthase and methylenetetrahydrofolate reduetase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol 2005 23 1365-1369. 

Methylenetetrahydrofolate reductase is an approximately 19,301 base pair gene with 11 exons and located on chromosome lp36.3 (2). Multiple polymorphic sites have been described, with the C677T and A1298G most often studied. As expected, allele frequency data varies by ethnicity The MTHFR C677T variant allele is present in 34% of Caucasians, 20% of Italians and Hispanics, 14% of African-Americans, and <1 % of Africans (3,4). The MTHFR A1298G allele is present in n%-36% of Western Europeans (4). 

Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies a HuGE review. Am JEpidemiol 2000 151 862-877. 

Matsushita S, Muramatsu T, Arai H, Matsui T, Higuchi S. The frequency of the methylenetetrahydrofolate reductase-gene mutation varies with age in the normal population. Am J Hum Genet 1997 61 1459-1460. 

Goyette R et al, Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/ phenotype correlations in severe methylenetetrahydrofolate reductase deficiency, Am J Hum Genet 1995 56(5) 1052-1059. 

Goyette R et al, Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR, Am J Hum Genet 1996 59(6) 1268-1275. 

Nishio H, et al, A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population. Jpn J Hum Genet I 996 41 (2) 247-251. 

Vilaseca MA, Monros E, Artuch R, Colome C, Farre C, Vails C, Cardo E, Pineda M. Anti-epileptic drug treatment in children hyperhomocysteinaemia, B-vitamins and the 677C T mutation of the methylenetetrahydrofolate reductase gene. Eur J Paediatr Neurol 2000 4(6) 269-77. 

Kluijtmans, L., Heuvel, L., Boers, G., Frosst, R, Stevens, E., Oost, B., Heijer, M., Trijbels, F., Rozen, R., and Blom, G. (19%). Molecular genetic analysis in mild hyperhomocyste-inemia A common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am. J. Hum. Genet. 58,35-41. 

Brattstrom L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteiiiemia but not to vascular disease the result of a meta-analysis. Circulation 1998 98 2520-6. 

Methylenetetrahydrofolate reductase (MTHFR) is encoded by the MTHFR gene located on chromosome lp36.22. It is the rate-limiting enzyme in the folic acid metabolic cycle that is critical for the... 

Etienne M C, Formento J L, Chazal M, et al. (2004). Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients. Pharmacogen. 14 785-792. 

Etienne, M. C., lie, K., Formento, J. L., et al. (2004) Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms relationships with 5-fluorouracil sensitivity. Br. J. Cancer 90, 526-534. 

Sell, S.M. and Lugemwa, P.R., Development of a highly accurate, rapid PCR-RFLPgenotyping assay for the methylenetetrahydrofolate reductase gene. Genet Test, 3, 287,1999. 

---