Association of maternal diabetes mellitus and UCP2 gene polymorphisms with congenital heart disease in offspring: a case-control study

Abstract

To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.