Department of Pediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia; Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
Environ Int. 2020 Jul;140:105610. doi: 10.1016/j.envint.2020.105610. Epub 2020 Apr 2.
Epidemiological studies have linked air pollutant to adverse health effects even at low exposure levels, but limited evidence is available on its associations with gene expression levels.
To investigate associations between air pollutants and gene expression levels.
We collected data from Brisbane System Genetics Study (BSGS) - a family-based system genetics study. Expression levels of candidate genes were obtained for whole blood from 266 pairs of twins (192 monozygotic and 74 dizygotic pairs) and 165 parents. Data on individual phenotypes were also obtained, including age, sex, Body Mass Index and exposure to smoke. Daily data on mean temperature and air pollutants, including particulate matter with aerodynamic diameter ≤2.5 μm (PM), ozone (O), nitrogen dioxide (NO) and sulfur dioxide (SO), were collected from seven monitoring stations for the day when the blood samples were collected. The association between each air pollutant and expression level of each gene was analyzed by using generalized linear models with adjustment for temperature and individual phenotypes, and its difference between monozygotic and dizygotic twins was investigated.
The mean value for daily concentration of air pollutants were 5.9 µg/m for PM, 16.3 ppb for O, 6.5 ppb for NO, and 1.4 ppb for SO, respectively. All air pollutants' levels in Brisbane during our study period were well under the National Air Quality Standard Air pollutant levels. We observed positive associations (false discovery rate [FDR]<0.1) among twins between PM and expression levels of HSPA8 and SOD1 and also between SO and AHR expression level. Negative associations were observed between SO and 11 genes among twins, including AHR, DUSP1, GEMIN4, GPX1, KLF2, PTGS2, TLR4, TNF, TNFRSF1B, TXNRD1, and XBP1, with most of them found at lag 0-7 days (FDR < 0.1). Furthermore, the association between SO and DUSP1 expression level was stronger among monozygotic twins than dizygotic twins (FDR < 0.1). We did not find strong evidence linking air pollutants to gene expression levels among parents.
Our findings require confirmation but suggest potential associations of expression levels at several genes with air pollutants at low exposure level and an individual's genetic background modifies the association between SO and DUSP1 gene, which may help bridge the gap of epidemiological studies with both in vivo and in vitro toxicological experiments and provide some insights into the role of nature-nurture of an individual in gene expression response to air pollutants.
即使在低暴露水平下，流行病学研究也将空气污染物与不良健康影响联系起来，但关于其与基因表达水平的关联的证据有限。
调查空气污染物与基因表达水平之间的关系。
我们从布里斯班系统遗传学研究（BSGS）中收集了数据，这是一项基于家庭的系统遗传学研究。从 266 对双胞胎（192 对同卵双胞胎和 74 对异卵双胞胎）和 165 对父母的全血中获得了候选基因的表达水平。还获得了个体表型的数据，包括年龄、性别、体重指数和吸烟暴露。收集了从七个监测站收集的与血液样本采集当天的日平均温度和空气污染物数据，包括空气动力学直径≤2.5μm（PM）、臭氧（O）、二氧化氮（NO）和二氧化硫（SO）的颗粒物。使用广义线性模型，根据温度和个体表型对每个空气污染物与每个基因表达水平的关系进行了分析，并对同卵双胞胎和异卵双胞胎之间的差异进行了调查。
空气污染物的日平均浓度分别为 5.9μg/m³PM、16.3ppb O、6.5ppb NO 和 1.4ppb SO。我们研究期间布里斯班的所有空气污染物水平都远低于国家空气质量标准。我们观察到双胞胎之间 PM 和 HSPA8 和 SOD1 表达水平之间以及 SO 和 AHR 表达水平之间存在正相关（假发现率[FDR] < 0.1）。双胞胎之间还观察到 SO 与 11 个基因之间的负相关，包括 AHR、DUSP1、GEMIN4、GPX1、KLF2、PTGS2、TLR4、TNF、TNFRSF1B、TXNRD1 和 XBP1，其中大多数在滞后 0-7 天（FDR < 0.1）发现。此外，SO 和 DUSP1 表达水平之间的关联在同卵双胞胎中强于异卵双胞胎（FDR < 0.1）。我们没有发现强有力的证据表明空气污染物与父母的基因表达水平之间存在关联。
我们的研究结果需要进一步证实，但表明几个基因的表达水平与低暴露水平下的空气污染物之间存在潜在关联，并且个体的遗传背景会改变 SO 和 DUSP1 基因之间的关联，这可能有助于弥合流行病学研究与体内和体外毒理学实验之间的差距，并为个体在空气污染物基因表达反应中的先天与后天作用提供一些见解。
