MTHFR
MEDIUMMethylenetetrahydrofolate reductase
Chromosome: 1p36.22
Gene Overview
MTHFR encodes methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for homocysteine remethylation. The C677T variant (rs1801133) reduces enzyme activity and raises homocysteine, especially when folate intake is low. Associated with cardiovascular disease, neural tube defects, and (controversially) depression. Folate and B-vitamin status are key environmental modifiers; gene–nutrient interactions are well documented.
Molecular Function
- folate metabolism
- homocysteine remethylation
- one-carbon metabolism
Protein class: oxidoreductase
Regulatory Annotation
Promoter activity: Constitutively expressed; nutrient-sensitive.
eQTL tissues: liver, blood
Tissue Expression Context
Pathways
No pathways linked.
Linked Diseases & Exposures
Diseases
- coronary-artery-disease— meta-analysis, strength 0.55
- hypertension— literature, strength 0.5
Exposures
- diet-quality— folate intake G×E, strength 0.85
Mechanistic Hypotheses
TT genotype increases homocysteine; low folate intake amplifies the effect and cardiovascular risk.
Meta-analyses; folate fortification studies.
MEDIUMConfidence Rating
Overall evidence confidence for this gene entry: MEDIUM
References
- 1.Clarke R, et al. (2012). MTHFR 677C>T and cardiovascular disease. Journal of the American Medical Association. doi:10.1001/jama.2012.1058