BACKGROUND Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures. OBJECTIVE Overall study goals were to investigate whole blood gene expression in smokers and non-smokers to examine associations between cigarette smoke and changes in gene expression by obesity status and test for effect modification. METHODS Relative fold-change in mRNA expression levels of 84 genes were analyzed using a Toxicity and Stress PCR array among 50 21-54 year old adults. Data on smoking status was confirmed using urinary cotinine levels. Adjusted models included age, gender, white blood cell count and body-mass index. RESULTS Models comparing gene expression of smokers vs. non-smokers identified six differentially expressed genes associated with smoking after adjustments for covariates. Obesity was associated with 29 genes differentially expressed compared to non-obese. We also identified 9 genes with significant smoking/obesity interactions influencing mRNA levels in adjusted models comparing expression between smokers vs non-smokers for four DNA damage related genes (GADD45A, DDB2, RAD51 and P53), two oxidative stress genes (FTH1, TXN), two hypoxia response genes (BN1P3lL, ARNT), and one gene associated with unfolded protein response (ATF6B). CONCLUSIONS Findings suggest that obesity alters human sensitivity to smoke exposures through several biological pathways by modifying gene expression. Additional studies are needed to fully understand the clinical impact of these effects, but risk assessments should consider underlying phenotypes, such as obesity, that may modulate sensitivity of vulnerable populations to environmental exposures.

中文翻译：

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吸烟者和非吸烟者之间的转录差异以及肥胖作为人类对环境暴露敏感性的危险因素的差异。


背景技术肥胖已被证明会改变对空气污染和吸烟的反应，但潜在的生物学机制在很大程度上是未知的，并且很少有研究探索肥胖增加人类对环境暴露的敏感性的机制。目的 总体研究目标是调查吸烟者和非吸烟者的全血基因表达，以检查香烟烟雾与肥胖状态导致的基因表达变化之间的关联，并测试效果修正。方法 使用毒性和应激 PCR 阵列分析 50 名 21-54 岁成年人中 84 个基因 mRNA 表达水平的相对倍数变化。吸烟状况的数据通过尿可替宁水平得到证实。调整后的模型包括年龄、性别、白细胞计数和体重指数。结果 比较吸烟者与非吸烟者基因表达的模型在调整协变量后发现了与吸烟相关的六个差异表达基因。与非肥胖者相比，肥胖与 29 个差异表达的基因相关。我们还确定了 9 个与吸烟/肥胖相互作用显着影响 mRNA 水平的基因，在调整后的模型中比较了吸烟者与非吸烟者之间四种 DNA 损伤相关基因（GADD45A、DDB2、RAD51 和 P53）、两种氧化应激基因（FTH1、TXN）的表达。 ，两个缺氧反应基因（BN1P3lL，ARNT）和一个与未折叠蛋白反应相关的基因（ATF6B）。结论 研究结果表明，肥胖通过改变基因表达，通过多种生物途径改变人类对烟雾暴露的敏感性。 需要进行更多研究来充分了解这些影响的临床影响，但风险评估应考虑潜在的表型，例如肥胖，这可能会调节弱势群体对环境暴露的敏感性。