Center for Life Course Health Research, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
Department of Medical Sciences, University of Turin, Turin, Italy; Italian Institute for Genomic Medicine, IIGM, Turin, Italy.
EBioMedicine. 2018 Dec;38:206-216. doi: 10.1016/j.ebiom.2018.10.066. Epub 2018 Nov 13.
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.
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).
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 × 10 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels.
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.
在胎儿期到成年期，DNA 甲基化在 GFI1 基因座与吸烟暴露之间的关联已被反复证实。我们探索了 DNA 甲基化是否是将母亲产前吸烟暴露与后代成人心血管代谢健康联系起来的一种机制。
我们对欧洲、澳大利亚和美国的 22 项基于人群的研究进行了荟萃分析，这些研究探讨了 GFI1 基因座的 DNA 甲基化与母亲产前吸烟、成年自身吸烟以及心血管代谢表型之间的关系（n=18212）。在全血中测量 GFI1 基因座的 DNA 甲基化。采用多变量回归模型来检验其与产前和成年自身吸烟的相关性。根据体重指数（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）来分析 DNA 甲基化水平。
有三个而非全部八个 GFI1-CpG 与母亲产前吸烟有关，而所有八个 CpG 与成年自身吸烟有关。与母体产前吸烟最强相关的 CpG 位点 cg14179389 的 DNA 甲基化水平较低，在调整性别、年龄和成年吸烟因素后，与 WC 和 BP 升高有关，校正后的 P 值<0.012。相比之下，与母体产前吸烟最强相关的 CpG 位点 cg09935388 的 DNA 甲基化水平较低，与 BMI、WC 和 BP 降低有关（校正后 1×10-5<P<0.01）。同样，cg12876356、cg18316974、cg09662411 和 cg18146737 等 CpG 位点的 DNA 甲基化水平较低与 BMI 和 WC 降低有关（5×10-5<P<0.001）。所有 CpG 位点的 DNA 甲基化水平较低与 TG 水平升高有关。
GFI1 上的表观遗传变化与宫内/成年期的吸烟暴露有关，并与心血管代谢危险因素密切相关。
欧盟地平线 2020 研究与创新计划，协议号 633595 DynaHEALTH。
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