|(G;G)||2||1.4x higher risk for meningiomas|
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.[PMID 18483342]
|Disease Association||Defects in MTRR are the cause of methylcobalamin deficiency type E (cblE) (MIM:236270); also known as vitamin B12- responsive homocystinuria or homocystinuria-megaloblastic anemia complementation type E. Patients who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hypomethioninemia, and hyperhomocysteinemia, a risk factor in cardiovascular disease and neural tube defects. It is an autosomal recessive disease.|
[PMID 19493349] 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects
[PMID 18682255] Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions
[PMID 20883119] Common polymorphisms in six genes of the methyl group metabolism pathway and obesity in European adolescents
[PMID 21211571] MTHFR and MTRR genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from the Czech Republic
[PMID 22005284] Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability
[PMID 21429654] Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility
[PMID 22796266] Polymorphisms of tumor-related genes IL-10, PSCA, MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population
[PMID 17035141] Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
[PMID 18191955] Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.
[PMID 18199722] Dietary vitamin B6 intake and the risk of colorectal cancer.
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[PMID 18521744] BRCA1 promoter methylation is associated with increased mortality among women with breast cancer.
[PMID 18708404] B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.
[PMID 18708408] Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.
[PMID 18936436] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
[PMID 18992148] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.
[PMID 19064578] No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk.
[PMID 19336559] Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.
[PMID 19376481] One-carbon metabolism and breast cancer: an epidemiological perspective.
[PMID 19657388] Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts.
[PMID 19706844] Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.
[PMID 19776626] Polymorphisms in methionine synthase, methionine synthase reductase and serine hydroxymethyltransferase, folate and alcohol intake, and colon cancer risk.
[PMID 20852008] Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.
[PMID 21349258] Folate and choline metabolism gene variants and development of uterine cervical carcinoma.
[PMID 21688148] Polymorphic variants of genes involved in homocysteine metabolism in celiac disease.
[PMID 22183302] Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population.
|Disease||Neural tube defects Down syndrome not specified Gastrointestinal stromal tumor methotrexate response - Toxicity/ADR|
|CLNDBN||Neural tube defects, folate-sensitive, susceptibility to Down syndrome, susceptibility to not specified Gastrointestinal stromal tumor methotrexate response - Toxicity/ADR|
|CLNSRC||OMIM Allelic Variant PharmGKB Clinical Annotation PharmGKB|
|CLNACC||RCV000007444.2, RCV000007445.2, RCV000126873.3, RCV000144926.1, RCV000211244.1,|
|qualified_impact||Low clinical importance, Likely pathogenic|
|summary||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" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). 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.|
[PMID 23401104] Folate-genetics and colorectal neoplasia: what we know and need to know next
[PMID 24261678] MTRR A66G polymorphism and leukemia risk: evidence from published studies
[PMID 22021659] Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.
[PMID 22706675] Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).
[PMID 23560644] Polymorphisms in genes involved in the free-radical process in patients with sudden sensorineural hearing loss and Meniere's disease.
[PMID 26196053] Association between genetic polymorphisms in folate-related enzyme genes and infertile men with non-obstructive azoospermia