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 1298C allele and using a periconception folic acid supplement.


CONCLUSIONS
The MTHFR C677T and A1298C polymorphisms are not strong risk factors for CHDs.
van Driel
Lydi M J W
LM
Department of Obstetrics and Gynecology/Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
Verkleij-Hagoort
Anna C
AC
de Jonge
Robert
R
Uitterlinden
André G
AG
Steegers
Eric A P
EA
van Duijn
Cornelia M
CM
Steegers-Theunissen
Régine P M
RP
D000328:Adult; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005838:Genotype; D006330:Heart Defects, Congenital / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009426:Netherlands; D012256:Riboflavin / Q000008:administration & dosage; D012307:Risk Factors
D005492:Folic Acid; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase; D012256:Riboflavin