Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
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DOI：
10.1016/j.ebiom.2018.10.066
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发表时间：
2018-12-01
期刊：
影响因子：
11.1
通讯作者：
Sebert, Sylvain
中科院分区：
文献类型：
--
作者：
Parmar, Priyanka;Lowry, Estelle;Sebert, Sylvain
背景：GFI1 位点的 DNA 甲基化反复与从胎儿期开始接触吸烟有关。我们探讨了 DNA 甲基化是否可能是一种将母亲产前吸烟暴露与后代成年心脏代谢健康联系起来的机制。方法：我们在来自欧洲、澳大利亚和美国的 22 项基于人群的研究 (n= 18,212) 中荟萃分析了 GFI1 位点 DNA 甲基化与母亲产前吸烟、成人自身吸烟和心脏代谢表型之间的关联。在全血中测量 GFI1 位点的 DNA 甲基化。拟合多变量回归模型来检查其与产前和成年吸烟暴露的关系。分析了 DNA 甲基化水平与体重指数 (BMI)、腰围 (WC)、空腹血糖 (FG)、高密度脂蛋白胆固醇 (HDL-C)、甘油三酯 (TG)、舒张压和收缩压 (BP) 的关系。结果：八个 GFI1-CpG 中的三个的 DNA 甲基化水平较低与母亲产前吸烟有关，而所有八个 CpG 都与成人自身吸烟有关。当针对性别、年龄和成人吸烟进行调整后，cg14179389（最强的母亲产前吸烟位点）的较低 DNA 甲基化与 WC 和 BP 增加相关，经 Bonferroni 校正的 P < 0.012。相比之下，cg09935388（最强的成年人自身吸烟位点）的 DNA 甲基化较低，与 BMI、WC 和 BP 降低相关（调整后 1 x 10(-7) < P < 0.01）。同样，cg12876356、cg18316974、cg09662411 和 cg18146737 处的较低 DNA 甲基化与 BMI 和 WC 降低相关 (5 x 10(-8) < P < 0.001）。所有 CpG 的较低 DNA 甲基化始终与较高的 TG 水平相关。解释：GFI1 的表观遗传变化与子宫内/成年期吸烟暴露有关，并与心脏代谢危险因素密切相关。基金：欧盟地平线 2020 研究和创新计划，根据资助协议编号。 633595 动态健康。 (c) 2018 年作者。由 Elsevier B.V. 出版
Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP).Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels.Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH. (c) 2018 The Authors. Published by Elsevier B.V.