Two MTHFR polymorphisms, maternal B-vitamin intake, and CHDs

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Nutritional Science

Background:

• Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are linked to congenital malformations.
• The association between MTHFR polymorphisms and congenital heart defects (CHDs) remains unclear.
• This study investigates MTHFR polymorphisms, folate, and vitamin B2 intake in relation to CHD risk.

Purpose of the Study:

• To determine if MTHFR C677T and A1298C polymorphisms are associated with congenital heart defects (CHDs).
• To examine the role of maternal dietary intake of folate and vitamin B2, as well as supplement use, in CHD risk.
• To analyze potential interactions between MTHFR genotypes, nutrient intake, and CHD development.

Main Methods:

• A case-control family study was conducted in the Netherlands with 230 cases and 251 control children.
• Maternal periconception folic acid supplement use and dietary intake of folate and vitamin B2 were assessed via questionnaires.
• All participants were genotyped for MTHFR C677T and A1298C polymorphisms; data were analyzed using logistic regression.

Main Results:

• MTHFR 677 CT and TT genotypes showed no significant increase in CHD risk across mothers, fathers, or children.
• The MTHFR 1298 CC genotype in fathers and the MTHFR 1298 AC genotype in children were associated with a reduced CHD risk.
• A significant interaction was observed where mothers with the MTHFR 1298C allele using periconception folic acid supplements had a nearly twofold increased risk of CHDs.

Conclusions:

• MTHFR C677T and A1298C polymorphisms are not identified as strong risk factors for congenital heart defects (CHDs).
• Maternal folic acid supplementation in the presence of the MTHFR 1298C allele warrants further investigation due to a potential interaction increasing CHD risk.