Chen Qian, Huang Peng, Song Xin-Li, Liu Yi-Ping, Sun Meng-Ting, Wang Ting-Ting, Zhang Sen-Mao, Qin Jia-Bi
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2022 Jul 15;24(7):797-805. doi: 10.7499/j.issn.1008-8830.2203002.
To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 () and methylenetetrahydrofolate dehydrogenase 2 () gene polymorphisms with congenital heart disease (CHD) in offspring.
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.
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).
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.
研究母亲亚甲基四氢叶酸脱氢酶1（）和亚甲基四氢叶酸脱氢酶2（）基因多态性与子代先天性心脏病（CHD）的关联。
进行一项基于医院的病例对照研究。将2017年11月至2020年3月期间在湖南省儿童医院就诊的683例单纯先天性心脏病患儿的母亲纳入病例组，将同期在同一医院就诊且无任何畸形的740例健康儿童的母亲纳入对照组。进行问卷调查以收集相关暴露数据，然后采集母亲的静脉血样本（5 mL）以检测和基因多态性。采用多因素logistic回归分析评估和基因多态性与先天性心脏病的关联。使用Haploview 4.2软件中的四配子检验构建单倍型并评估单倍型与先天性心脏病之间的关联。采用广义多因素降维法和logistic回归分析来检验基因-基因相互作用及其与先天性心脏病的关联。
多因素logistic回归分析显示，母亲rs11849530位点的基因多态性（GA与AA相比：=1.49；GG与AA相比：=2.04）以及rs1256142位点的（GA与GG相比：=2.34；AA与GG相比：=3.25）显著增加子代患先天性心脏病的风险（<0.05），而母亲rs1950902位点的基因多态性（AA与GG相比：=0.57）以及rs1095966位点的基因多态性（CA与CC相比：=0.68）显著降低子代患先天性心脏病的风险（<0.05）。母亲中G-G-G（=1.86）和G-A-G（=1.35）的单倍型显著增加子代患先天性心脏病的风险（<0.05）。基因-基因相互作用分析显示，rs1950902与rs2236222之间的一阶相互作用以及涉及rs1950902、rs1256142和rs1095966的二阶相互作用可能与先天性心脏病风险相关（<0.05）。
母亲的和基因多态性及其单倍型，以及rs1950902与rs2236222之间以及rs1950902、rs1256142和rs1095966之间的相互作用与子代先天性心脏病风险相关。
