[Association of maternal and gene polymorphisms with congenital heart disease in offspring].

Objectives: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 () and methylenetetrahydrofolate dehydrogenase 2 () gene polymorphisms with congenital heart disease (CHD) in offspring.

Methods: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect and gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of and gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD.

Results: The multivariate logistic regression analysis showed that maternal gene polymorphisms at rs11849530 (GA vs AA: =1.49; GG vs AA: =2.04) andat rs1256142 (GA vs GG: =2.34; AA vs GG: =3.25) significantly increased the risk of CHD in offspring (<0.05), while maternal gene polymorphisms at rs1950902 (AA vs GG: =0.57) and gene polymorphisms at rs1095966 (CA vs CC: =0.68) significantly reduced the risk of CHD in offspring (<0.05). The haplotypes of G-G-G (=1.86) and G-A-G (=1.35) in mothers significantly increased the risk of CHD in offspring (<0.05). The gene-gene interaction analyses showed that the first-order interaction between rs1950902 and rs2236222 and the second-order interaction involving rs1950902, rs1256142, and rs1095966 might be associated with risk of CHD (<0.05).

Conclusions: Maternal and gene polymorphisms and their haplotypes, as well as the interaction between rs1950902 and rs2236222 and between rs1950902, rs1256142, and rs1095966, are associated with the risk of CHD in offspring.