|(C;T)||1.25||Possible increased risk of birth defects|
|(T;T)||1.5||Slightly (~1.5x) higher risk for Caucasian mothers to give birth to NTD children|
The Arg653Gln mutation was studied and found not to affect the enzyme activity when present, but did seem to decrease the half-life and stability. [PMID 18767138]
A study in Quebec showed an association in children with mutations in MTHFD1 having increased risk for heart defects, possibly in a folate status dependent manner (IE more so if their mother was not getting enough folate during pregnancy). [PMID 18767138]
A 2014 meta-analysis of nine studies totaling 4,302 cases of children born with neural tube defects concluded that Caucasian mothers carrying rs2236225(C;T) or rs2236225(T;T) alleles were at increased risk, of about 1.5 - 1.7x, of having affected children compared to mothers with no (T) alleles. However, they cautioned that their results should be "viewed with caution" given the statistical uncertainties inherent in these studies. [PMID 24977710][PMID 19130090] rs1076991 C > T exerts a significant effect on promoter activity in vitro and along with rs2236225 G > A influences embryonic development.
|Disease Association||Defects in MTHFD1 may be associated with elevated risk for neural tube defects (NTD) such as spina bifida.|
[PMID 20217437] Association analysis of CbetaS 844ins68 and MTHFD1 G1958A polymorphisms with Alzheimer's disease in Chinese
[PMID 21429654] Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility
|Disease||Neural tube defects not specified|
|CLNDBN||Neural tube defects, folate-sensitive, susceptibility to not specified|
|CLNSRC||OMIM Allelic Variant|
[PMID 27342765] Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.
[PMID 16816108] Common genetic polymorphisms affect the human requirement for the nutrient choline.
[PMID 17035141] Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
[PMID 17613168] Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline.
[PMID 17616785] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not.
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[PMID 18221821] Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population.
[PMID 18661527] Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.
[PMID 18789905] Genetic polymorphisms in methyl-group metabolism and epigenetics: lessons from humans and mouse models.
[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 19112534] Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.
[PMID 19167960] Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted.
[PMID 19261726] Epigenetic mechanisms for nutrition determinants of later health outcomes.
[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.
[PMID 19493349] 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.
[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 19808787] Genetics of human neural tube defects.
[PMID 20018050] Application of sex-specific single-nucleotide polymorphism filters in genome-wide association data.
[PMID 20565774] Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.
[PMID 20890936] Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population.
[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.
|qualified_impact||Insufficiently evaluated pharmacogenetic|
[PMID 24254627] MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the brazilian population
[PMID 22903727] Maternal and infant gene-folate interactions and the risk of neural tube defects.
[PMID 25039261] Association Study of MTHFD1 Coding Polymorphisms R134K and R653Q With Migraine Susceptibility
[PMID 25074646] Associations of Common Variants in Methionine Metabolism Pathway Genes with Plasma Homocysteine and the Risk of Type 2 Diabetes in Han Chinese
[PMID 25921832] Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort