Breton Carrie V, Gao Lu, Yao Jin, Siegmund Kimberly D, Lurmann Fred, Gilliland Frank
University of Southern California, Dept of Preventive Medicine, 2001 N Soto St, Los Angeles, CA 90089, USA.
Sonoma Technology Inc, 1455 N. McDowell Blvd, Suite D, Petaluma, CA 94954-6503, USA.
Environ Epigenet. 2016 Jun 12;2(2):dvw005. doi: 10.1093/eep/dvw005. eCollection 2016 Apr.
Ambient air pollution is associated with adverse health outcomes including cardio-respiratory diseases. Epigenetic mechanisms such as DNA methylation may play a role in driving such associations. We investigated the effects of prenatal particulate matter (PM) exposure on DNA methylation of 178,309 promoter regions in 240 newborns using the Infinium HumanMethylation450 BeadChip, using a generalized linear regression model with a quasi-binomial link family, adjusted for gender, plate, and cell types. PM-associated CpG loci were then investigated for their associations with childhood asthma, carotid intima-media thickness (CIMT), and blood pressure (BP) using logistic or linear regression. Thirty-one loci were associated with either PM or PM using FDR-corrected p-values of less than 0.15. Two loci were evaluated for replication in a separate population of 280 Children's Health Study (CHS) subjects using Pyrosequencing, of which one successfully replicated (COLEC11 cg03579365). Three of the 31 loci were also associated with physician-diagnosed asthma at 6 years old, two were associated with CIMT and one with systolic BP at 10 years old. A higher methylation level in TM9SF2 (cg02015529) and UBE2S (cg00035623), respectively, was associated with a 2SD increase in prenatal PM and was also associated with 36% and 98% increased odds of asthma; whereas methylation of TDRD6 (cg22329831) was negatively associated with PM and a 24% decreased odds of asthma. Prenatal PM exposure was associated with altered DNA methylation in newborn blood in a small number of gene promoters, some of which were also associated with cardio-respiratory health outcomes later in childhood. : methylation, particulate matter, air pollution, asthma, cardiovascular.
环境空气污染与包括心肺疾病在内的不良健康后果相关。DNA甲基化等表观遗传机制可能在推动此类关联中发挥作用。我们使用Infinium HumanMethylation450 BeadChip，通过具有拟二项链接族的广义线性回归模型，对240名新生儿178,309个启动子区域的DNA甲基化进行了研究，并对性别、芯片板和细胞类型进行了校正。然后使用逻辑回归或线性回归研究了与PM相关的CpG位点与儿童哮喘、颈动脉内膜中层厚度（CIMT）和血压（BP）之间的关联。使用错误发现率（FDR）校正后的p值小于0.15，有31个位点与PM或PM相关。使用焦磷酸测序法在另外280名儿童健康研究（CHS）受试者中评估了两个位点的重复性，其中一个成功重复（COLEC11 cg03579365）。31个位点中的3个也与6岁时医生诊断的哮喘相关，2个与CIMT相关，1个与10岁时的收缩压相关。TM9SF2（cg02015529）和UBE2S（cg00035623）中较高的甲基化水平分别与产前PM增加2个标准差相关，也与哮喘几率增加36%和98%相关；而TDRD6（cg22329831）的甲基化与PM呈负相关，哮喘几率降低24%。产前PM暴露与少数基因启动子中新生儿血液中DNA甲基化改变有关，其中一些也与儿童后期的心肺健康结果相关。：甲基化、颗粒物、空气污染、哮喘、心血管。
