Department of Preventive Medicine, Feinberg School of Medicine; Northwestern University, Chicago, IL, USA.
Mary Ann and J. Milburn Smith Child Health Research, Outreach, and Advocacy Center, Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital, Chicago, IL, USA.
Child Obes. 2021 Jul;17(5):365-370. doi: 10.1089/chi.2020.0327. Epub 2021 Apr 6.
Gestational diabetes mellitus (GDM) is a major macrosomia risk factor. Variations in the catechol--methyltransferase (COMT; rs4680) genotypes are associated with heightened susceptibility to environmental exposures and nutritional conditions. However, macrosomia risks associated with COMT genetics, epigenetics, and the interaction between genetic and epigenetics among children with and without exposure to GDM are unknown. Data from women/children pairs ( = 1087) who participated in the Tianjin Gestational Diabetes Birth Cohort were used to examine the odds of being born with macrosomia associated with COMT-genotypes, 55 CpG sites located on the COMT gene, and genetic and epigenetic interactions. Odds of macrosomia associated with COMT genetic, epigenetic, genetic and epigenetic interactions, and moderations with GDM were tested using adjusted logistic regression models. Overall, 16.1% ( = 175) of children were born with macrosomia. Models showed that children with at least one copy of the minor allele (A) had higher odds of macrosomia (odds ratio, 1.82; 95% confidence interval 1.25-2.64) compared with children with the GG-genotype. After false discovery rate corrections, none of the 55 CpG sites located on the COMT gene was associated with odds of macrosomia. The genetic and epigenetic associations were not modified by exposure to GDM. Findings suggest carriers of the COMT GG-genotype had lower odds of macrosomia, and this association was not modified by epigenetics or exposure to GDM.
妊娠期糖尿病（GDM）是巨大儿的一个主要危险因素。儿茶酚-O-甲基转移酶（COMT；rs4680）基因型的变异与对环境暴露和营养条件的敏感性增加有关。然而，与 COMT 遗传、表观遗传以及 GDM 暴露与未暴露儿童的遗传与表观遗传之间相互作用相关的巨大儿风险尚不清楚。本研究使用参加天津妊娠期糖尿病出生队列的妇女/儿童对（n=1087）的数据，来检验 COMT 基因型、位于 COMT 基因上的 55 个 CpG 位点以及遗传和表观遗传相互作用与巨大儿发生几率之间的关联。使用调整后的逻辑回归模型检验了与 COMT 遗传、表观遗传、遗传与表观遗传相互作用以及 GDM 调节相关的巨大儿发生几率。总体而言，16.1%（n=175）的儿童出生时为巨大儿。模型显示，与 GG 基因型的儿童相比，至少携带一个次要等位基因（A）的儿童发生巨大儿的几率更高（比值比，1.82；95%置信区间 1.25-2.64）。在经过错误发现率校正后，位于 COMT 基因上的 55 个 CpG 位点中没有一个与巨大儿发生几率相关。遗传和表观遗传的关联不受 GDM 暴露的影响。研究结果表明，COMT GG 基因型携带者发生巨大儿的几率较低，这种关联不受表观遗传学或 GDM 暴露的影响。
