Neophytou Andreas M, Oh Sam S, Hu Donglei, Huntsman Scott, Eng Celeste, Rodríguez-Santana José R, Kumar Rajesh, Balmes John R, Eisen Ellen A, Burchard Esteban G
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California.
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado.
Environ Epidemiol. 2019 Jun 19;3(3):e048. doi: 10.1097/EE9.0000000000000048. eCollection 2019 Jun.
Maternal smoking during pregnancy is a risk factor for chronic disease later in life and has been associated with variability of DNA methylation at specific cytosine-phosphate-guanine (CpG) loci. We assessed the role of DNA methylation as a potential mediator of adverse effects of in utero tobacco smoke exposures on asthma outcomes in Latino children from the US mainland and Puerto Rico.
Relationships between self-reported exposure and DNA methylation at CpG loci previously reported to be associated with maternal smoking were assessed in a subsample consisting of 572 children aged 8-21 years (310 cases with asthma, 262 healthy controls), sampled from a larger asthma case-control study. Subsequently, we assessed associations between top loci and asthma-related outcomes, followed by mediation analysis for loci for which associations with outcomes were observed.
Self-reported maternal smoking was associated with a -1.5% (95% confidence interval (CI) = -2.4%, -0.6%) lower methylation at CpG locus cg05575921 on the gene; a 1% increase in DNA methylation at the same locus resulted in an odds ratio (OR) of 0.90 (95% CI = 0.83, 0.96) for the odds of asthma. The OR for the indirect effect of maternal smoking on asthma mediated through methylation at the cg05575921 locus was 1.18 (95% CI = 1.07, 1.68), compared to the OR for the total effect of exposure in the parent study of 1.48 (95% CI = 1.03, 2.11).
Our findings suggest potential mediation by DNA methylation in the association between maternal smoking during pregnancy and asthma status.
孕期母亲吸烟是儿童日后患慢性病的一个风险因素，且与特定胞嘧啶-磷酸-鸟嘌呤（CpG）位点的DNA甲基化变异有关。我们评估了DNA甲基化作为子宫内烟草烟雾暴露对美国本土和波多黎各拉丁裔儿童哮喘结局不良影响的潜在介导因素的作用。
在一项更大规模的哮喘病例对照研究中抽取的一个子样本中，评估了自我报告的暴露与先前报道的与母亲吸烟相关的CpG位点DNA甲基化之间的关系，该子样本包括572名8 - 21岁的儿童（310例哮喘患儿，262名健康对照）。随后，我们评估了顶级位点与哮喘相关结局之间的关联，接着对观察到与结局有关联的位点进行中介分析。
自我报告的母亲吸烟与基因上CpG位点cg05575921处甲基化降低1.5%（95%置信区间（CI）= -2.4%，-0.6%）相关；同一位点DNA甲基化增加1%导致哮喘患病几率的比值比（OR）为0.90（95% CI = 0.83，0.96）。与母研究中暴露的总效应的OR为1.48（95% CI = 1.03，2.11）相比，母亲吸烟通过cg05575921位点甲基化对哮喘的间接效应的OR为1.18（95% CI = 1.07，1.68）。
我们的研究结果表明，DNA甲基化可能在孕期母亲吸烟与哮喘状态之间的关联中起介导作用。
