Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.5.1.20 (
methylenetetrahydrofolate reductase
)
2,134
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Genetic disturbances in folate metabolism may increase risk for congenital heart defects. We examined the association of heart defects with four polymorphisms in folate-related genes (
methylenetetrahydrofolate reductase
(
MTHFR
) c.677C.T,
MTHFR
c.1298A.C, methionine synthase reductase (MTRR) c.66A.G, and reduced folate carrier (SLC19A1) c.80A.G) in a case-control study of children (156 patients, 69 controls) and mothers of children with heart defects (181 patients, 65 controls), born before folic acid fortification. MTRR c.66A.G in children modified odds ratios for overall heart defects, specifically ventricular septal defect and
aortic valve stenosis
(p-value below 0.05). The 66GG and AG genotypes were associated with decreased odds ratios for heart defects (0.42, 95% confidence interval (0.18-0.97) and 0.39 (0.18-0.84), respectively). This overall association was driven by decreased risk for ventricular septal defect for 66GG and AG (odds ratio 0.32 (0.11-0.91) and 0.25 (0.09-0.65)) and decreased odds ratio for
aortic valve stenosis
for 66AG (0.27 (0.09-0.79)). The association of ventricular septal defect and 66AG remained significant after correction for multiple testing (p = 0.0044, multiple testing threshold p = 0.0125). Maternal
MTHFR
1298AC genotype was associated with increased odds ratio for
aortic valve stenosis
(2.90 (1.22-6.86), p = 0.0157), but this association did not meet the higher multiple testing threshold. No association between
MTHFR
c.677C.T or SLC19A1 c.80A.G and heart defect risk was found. The influence of folate-related polymorphisms may be specific to certain types of heart defects; larger cohorts of mothers and children with distinct sub-classes are required to adequately address risk.
...
PMID:Risk of congenital heart defects is influenced by genetic variation in folate metabolism. 2247 73
