Objective: 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.
Methods: 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.
Results: 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).
Conclusions: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.
目的: 探讨母亲糖尿病、解偶联蛋白2基因（UCP2）多态性及两者的交互作用与子代先天性心脏病（CHD）的关系。
方法: 采用以医院为基础的病例对照研究，选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组，选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查，收集相关暴露信息，同时采集母亲静脉血5 mL，用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。
结果: 多因素logistic回归分析显示，在控制混杂因素后，患有妊娠期糖尿病（OR=2.96，95% CI：1.57~5.59）、有妊娠期糖尿病史（OR=3.16，95% CI：1.59~6.28）和妊娠前患有糖尿病（OR=4.52，95% CI：2.41~8.50）均显著增加子代CHD的风险（P < 0.05）。母亲UCP2基因两个位点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）和rs660339（A/A vs G/G：OR=2.19，95% CI：1.34~3.58）的多态性与子代CHD的风险存在关联（P < 0.05）。交互作用分析显示，UCP2基因两个位点（rs659366和rs660339）的多态性与母亲糖尿病在子代CHD发生中存在交互作用（P < 0.05）。
结论: 母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。