Two MTHFR polymorphisms, maternal B-vitamin intake, and CHDs
BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with complex congenital malformations. Whether these polymorphisms are associated with CHDs is not clear. We studied both MTHFR polymorphisms, folate and vitamin B2 by maternal food intake and supplements, and CHD risk. METHODS: A case-control family study was conducted in a European population in the Netherlands including 230 case and 251 control children with both parents. Approximately 17 months after the index pregnancy, mothers filled out standardized questionnaires on periconception use of folic acid supplements and a validated food frequency questionnaire on current dietary folate and vitamin B2 intake. All subjects were genotyped for the MTHFR C677T and A1298C polymorphisms. Data were analyzed by logistic regression analysis and ORs and 95% CIs were calculated. For the interaction analysis the dominant model was used. RESULTS: The risk estimates for the MTHFR 677 CT genotypes were 1.4 (0.9-2.0) in mothers, 1.1 (0.8-1.6) in fathers, and 1.2 (0.8-1.7) in children, and for the MTHFR 677 TT genotypes 0.9 (0.6-1.2), 1.4 (1.0-1.9), and 1.0 (0.7-1.3), respectively. The MTHFR 1298 CC genotype in fathers and the MTHFR 1298 AC genotype in children significantly reduced CHD risk, 0.6 (0.5-0.9) and 0.6 (0.4-0.9), respectively. Of interest is the significant interaction (p = .008) towards a nearly twofold increased risk in mothers carrying the MTHFR 1298 C allele and using a periconception folic acid supplement. CONCLUSIONS: The MTHFR C677T and A1298C polymorphisms are not strong risk factors for CHDs.