[Association of maternal dietary intake, folic acid supplementation and offspring betaine-homocysteine methyltransferase (BHMT) and BHMT2 gene polymorphisms with congenital heart disease].

Objective

To evaluate the associations of maternal dietary intake, folic acid supplementation, offspring BHMT and BHMT2 gene polymorphisms and their interactions with the risk for congenital heart disease (CHD) and its main subtypes.

Methods

A hospital-based case control study was conducted. From January 2018 to May 2019, a total of 620 children with simple CHD and their mothers were consecutively recruited as the case group from Hunan Children's Hospital. During the same period, 620 children without any congenital anomalies and their mothers, who were diagnosed at the same hospital, were enrolled as the control group. The information about their demographic characteristics and periconceptional exposure information were collected by using structured questionnaire. In addition, peripheral venous blood samples were obtained from the children for genotyping of BHMT and BHMT2 polymorphisms. Multivariable logistic regression analysis and crossover analyses were conducted to evaluate the associations of maternal dietary intake, folic acid supplementation, offspring BHMT and BHMT2 gene polymorphisms and their interactions with the risk for CHD and its subtypes.

Results

After correction for multiple testing, multivariable logistic regression analyses showed that maternal excessive intakes of smoked food, barbecued food, fried food, pickled vegetable during early pregnancy was associated with increased risk for overall CHD in offspring [aOR>1.00, false discovery rate (FDR)-adjusted P<0.05], while maternal regular intakes of fish and shrimp, fresh egg, bean, milk product as well as periconceptional folic acid supplementation were associated with reduced risk for offspring overall CHD (aOR<1.00, FDR-adjusted P<0.05). Significant associations were observed between BHMT polymorphisms and overall CHD risk, including rs3733890 (AA vs. GG, aOR=2.61, 95%CI: 1.52-4.50), rs1316753 (recessive model, aOR= 1.63, 95%CI: 1.17-2.29), and rs1915706 (CC vs. TT, aOR=2.72, 95%CI: 1.42-5.21), similar results were also found in atrial septal defect and ventricular septal defect population. Moreover, BHMT gene polymorphisms showed antagonistic interactions with the intake of fish and shrimp, as well as bean (aOR<1.00, relative excess risk of interaction <0).

Conclusions

Maternal dietary patterns, folic acid supplementation, and BHMT gene polymorphisms (rs3733890, rs1316753, and rs1915706) are associated with the risk for CHD and its subtypes. In addition, interactions between BHMT polymorphisms and maternal dietary intake might contribute to the development of CHD in offspring.