Background

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.

Aim

To investigate associations between air pollutants and gene expression levels.

Methods

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_2.5), ozone (O₃), nitrogen dioxide (NO₂) and sulfur dioxide (SO₂), 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.

Results

The mean value for daily concentration of air pollutants were 5.9 µg/m³ for PM_2.5, 16.3 ppb for O₃, 6.5 ppb for NO₂, and 1.4 ppb for SO₂, 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 [$\mathit{FDR}]<0.1$) among twins between PM_2.5 and expression levels of HSPA8 and SOD1 and also between SO₂ and AHR expression level. Negative associations were observed between SO₂ 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 SO₂ 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.

Conclusion

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 SO₂ 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.

中文翻译：

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应对低水平空气污染的候选基因表达。

背景

流行病学研究已将空气污染物与不良健康影响联系在一起，即使在低暴露水平下也是如此，但是关于其与基因表达水平的关联的可用证据有限。

目标

调查空气污染物和基因表达水平之间的关联。

方法

我们从布里斯班系统遗传学研究（BSGS）收集了数据，该研究是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对同卵双胞胎对）和165个亲本中获得全血候选基因的表达水平。还获得了有关个体表型的数据，包括年龄，性别，体重指数和烟尘暴露。有关平均温度和空气污染物的每日数据，包括空气动力学直径≤2.5μm（PM _2.5）的颗粒物，臭氧（O ₃），二氧化氮（NO ₂）和二氧化硫（SO _2））是在采集血样当天从七个监测站采集的。通过调节温度和个体表型的广义线性模型分析每种空气污染物与每个基因表达水平之间的关联，并研究其在单卵双卵和双卵双卵之间的差异。

结果

PM _2.5的空气污染物日浓度平均值分别为5.9 µg / m ³，O ₃的平均值为16.3 ppb，NO ₂的平均值为6.5 ppb，SO ₂的平均值为1.4 ppb 。在我们的研究期间，布里斯班的所有空气污染物水平均远低于《国家空气质量标准》空气污染物水平。我们观察到正关联（错误发现率[$\mathit{罗斯福}]<0.1$PM _2.5与HSPA8和SOD1的表达水平之间以及SO ₂与AHR的表达水平之间的双胞胎之间）。在双胞胎中，SO ₂和11个基因之间存在负关联，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）被发现<0.1）。此外，单卵双胞胎中SO ₂和DUSP1表达水平之间的关联强于双卵双胞胎（FDR <0.1）。我们没有找到强有力的证据将父母之间的空气污染物与基因表达水平联系起来。

结论

我们的发现需要证实，但建议在几个基因的表达水平与低暴露水平的空气污染物之间的潜在关联，并且个人的遗传背景会修饰SO ₂和DUSP1基因之间的关联，这可能有助于弥合流行病学研究在体内和体内的差距。体外毒理学实验，并为个体自然营养在对空气污染物的基因表达反应中的作用提供了一些见识。