母亲还原叶酸载体基因多态性与子代先天性心脏病关联的病例对照研究

目的 探讨母亲还原叶酸载体（reduced folate carrier，RFC）基因多态性与子代先天性心脏病（congenital heart disease，CHD）的关系。方法 采用基于医院的病例对照研究，以2017年11月至2020年3月于湖南省儿童医院心胸外科就诊的683例CHD婴儿的母亲为病例组，以同期在该院就诊并排除任何畸形的740例婴儿的母亲为对照组。使用调查问卷收集研究对象的暴露资料，并采集产妇5 mL静脉血用于基因多态性检测。采用多因素logistic回归分析RFC基因多态性及其单倍型与CHD的关联，并采用广义多因子降维法分析基因-基因间交互作用。结果 多因素logistic回归显示，在控制混杂因素后，母亲RFC基因2个位点rs2236484（AG vs AA：OR=1.91，95%CI：1.45~2.51；GG vs AA：OR=1.96，95%CI：1.40~2.75）和rs2330183（CT vs CC：OR=1.39，95%CI：1.06~1.83）的多态性与子代CHD风险存在关联。母亲携带单倍型G-G（OR=1.21，95%CI：1.03~1.41）和T-G（OR=1.25，95%CI：1.07~1.46）显著增加子代CHD的风险。交互作用分析显示，RFC基因各位点在CHD发生中存在交互作用（P < 0.05）。结论 母亲RFC基因多态性及各位点间的交互作用与子代CHD的发生相关。

Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study

Objective To study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring. Methods A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions. Results After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05). Conclusions Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.