Risk factors and methylenetetrahydrofolate reductase gene in congenital heart disease.

Background: Congenital heart disease (CHD), which involve congenital cardiovascular malformations that occur during an embryo stage, may be the result of a complex interaction between genetic factors and environmental factors. The homozygous 677 T/T MTHFR gene and potential factors have been associated with CHD. Our objective was to study associations between potential environmental risk factors and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in CHD.

Methods: A total of 346 children with CHD and 237 healthy children were recruited. Their parents were also enlisted in the study and interviewed face-to-face to identify potential environmental risk factors. The MTHFR genotype was analyzed by restriction fragment length polymorphism (RFLP). Interactions between environmental risk factors and MTHFR gene polymorphisms were evaluated by the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S).

Results: There were significant differences in the occupational statuses of the mothers and their levels of drug exposure during gestation between the controls and the cases (P<0.05). These differences significantly increased offspring CHD risk (occupation: OR =5.45, 95% CI: 3.46-8.58; drug exposure: OR =4.91, 95% CI: 2.18-11.09). The frequency of the MTHFR gene 677 TT polymorphism in the mothers who had offspring with CHD was significantly different from that in the non-CHD controls (P<0.05). The frequency of this polymorphism also significantly differed between the children with CHD and the control group (P<0.05). An interaction was identified between the presence of the homozygous 677 TT genotype in the children and the mothers' occupational statuses (RERI =9.43, CI: 0.06-18.91).

Conclusions: A significant interaction was found between the homozygous 677 T/T MTHFR gene in children and the maternal occupational status and level of drug exposure during gestation. Avoiding or reducing the exposure of the risk factors mentioned above, strengthening pre-pregnancy checkups and guidance might help to reduce the risk of CHD.