背景:妊娠期糖尿病(GDM)和2型糖尿病(T2DM)共有许多病理生理因素,包括遗传学,但是表观遗传标记是否共享是未知的。我们旨在测试T2DM的DNA甲基化风险评分(MRS)是否与GDM相关。
方法:在两个独立的妊娠队列中,EPIPREG(n=480)和EPIDG(n=32),在28±2的胎龄测量外周血白细胞中的DNA甲基化。我们基于发表的T2DM全基因组关联研究(EWAS)的CpG命中,构建了EPIPREG和EPIDG的MRS。
结果:使用EPIPREG和EPIDG的混合模型逻辑回归,T2DM的MRS与GDM相关:奇数比(OR)[95%CI]:1.3[1.1-1.8],未调整模型的P=0.002,和1.4[1.1-1.7],对于按年龄调整的模型,P=0.00014,孕前BMI,糖尿病家族史和吸烟状况。此外,我们通过荟萃分析发现了6个CpG(cg14020176,cg22650271,cg14870271,cg27243685,cg06378491,cg25130381)与GDM相关,它们的一些甲基化定量位点(mQTLs)与T2DM和GDM有关。
结论:第一次,我们显示T2DM的DNA甲基化标记也与GDM相关,提示GDM和T2DM之间有共同的表观遗传机制。
Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria.
In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM.
With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1-1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1-1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM.
For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM.