rs1801394

rs1801394, also known as A66G or Ile22Met, is a SNP in the methionine synthase reductase MTRR gene. This gene encodes one of the two enzymes involved in the production of methionine (the other is MTR). The protein encoded by an rs1801394 allele has a lower affinity for MTR () and is inconsistently associated with homocysteine level, although it is a risk factor for neural tube defects () and Down syndrome () in conditions of higher homocysteine. Based on a study of British patients with primary brain tumors, (1,005 glioma cases and 631 meningioma cases), rs1801394(G;G) individuals were at higher risk for meningioma (odds ratio 1.41, CI: 1.02-1.94). In general, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk for these types of brain cancer. Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools. Dietary vitamin B6 intake and the risk of colorectal cancer. Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts. BRCA1 promoter methylation is associated with increased mortality among women with breast cancer. B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer. Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation. Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994. Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study. No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk. Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. One-carbon metabolism and breast cancer: an epidemiological perspective. Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Polymorphisms in methionine synthase, methionine synthase reductase and serine hydroxymethyltransferase, folate and alcohol intake, and colon cancer risk. Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. Folate and choline metabolism gene variants and development of uterine cervical carcinoma. Polymorphic variants of genes involved in homocysteine metabolism in celiac disease. Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population.

G;G

This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (for the Ile to Met substitution at amino acid 22). Mothers homozygous for this variant were found in a few studies to have an increased risk for Down syndrome babies (risk of 0.4%, average risk in population is 0.25%), but other studies (including in Italian, Irish, French, and Indian-Gujarati women) found no increased risk. Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and, it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.