Levinsson Anna, Olin Anna-Carin, Modig Lars, Dahgam Santosh, Björck Lena, Rosengren Annika, Nyberg Fredrik
Occupational and Environmental Medicine, Department of Public Health & Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, University of Umeå, Umeå, Sweden.
PLoS One. 2014 Jun 10;9(6):e99043. doi: 10.1371/journal.pone.0099043. eCollection 2014.
Experimental and epidemiological studies have reported associations between air pollution exposure, in particular related to vehicle exhaust, and cardiovascular disease. A potential pathophysiological pathway is pollution-induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and GSTCD, may contribute to determining individual susceptibility to air pollution as a promoter of coronary vulnerability.
We aimed to investigate effects of long-term traffic-related air pollution exposure, as well as variants in GSTP1, GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension. In addition, we studied whether air pollution effects were modified by the investigated genetic variants.
Genotype data at 7 single nucleotide polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD genes, as well as air pollution exposure estimates, were available for 119 AMI cases and 1310 randomly selected population controls. Population control individuals with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or on daily antihypertensive medication were defined as hypertensive (n = 468). Individual air pollution exposure levels were modeled as annual means of NO₂ (marker of vehicle exhaust pollutants) using central monitoring data and dispersion models, linking to participants' home addresses.
Air pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04-3.03) per 10 µg/m³ of long-term NO₂ exposure. Three GSTP1 SNPs were significantly associated with hypertension. The effect of air pollution on risk of AMI varied by genotype strata, although the suggested interaction was not significant. We saw no obvious interaction between genetic variants in the GST genes and air pollution exposure for hypertension.
Air pollution exposure entails an increased risk of AMI, and this risk differed over genotype strata for variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically-significantly.
实验和流行病学研究报告了空气污染暴露，特别是与汽车尾气相关的暴露，与心血管疾病之间的关联。一条潜在的病理生理途径是污染诱导的肺部氧化应激，并伴有继发性全身炎症。参与氧化应激的基因（如GSTP1、GSTT1和GSTCD）中的基因多态性，可能有助于确定个体对空气污染的易感性，空气污染是冠状动脉易损性的一个促进因素。
我们旨在研究长期交通相关空气污染暴露以及GSTP1、GSTT1和GSTCD基因变异对急性心肌梗死（AMI）和高血压风险的影响。此外，我们研究了所研究的基因变异是否会改变空气污染的影响。
GSTP1基因中7个单核苷酸多态性（SNP）以及GSTT1和GSTCD基因各1个的基因型数据，以及空气污染暴露估计值，可用于119例AMI病例和1310名随机选择的人群对照。收缩压≥140 mmHg、舒张压≥90 mmHg或正在服用每日抗高血压药物的人群对照个体被定义为高血压患者（n = 468）。使用中央监测数据和扩散模型，将个体空气污染暴露水平建模为二氧化氮（汽车尾气污染物的标志物）的年平均值，并与参与者的家庭住址相关联。
空气污染与AMI风险显著相关：长期二氧化氮暴露每增加10 µg/m³，比值比为1.78（95%置信区间1.04 - 3.03）。GSTP1基因的三个SNP与高血压显著相关。空气污染对AMI风险的影响因基因型分层而异，尽管所提示的相互作用不显著。我们未发现GST基因中的基因变异与空气污染暴露对高血压的明显相互作用。
空气污染暴露会增加AMI风险，并且对于GSTP1、GSTT1和GSTCD基因变异，这种风险在基因型分层上有所不同，尽管差异无统计学意义。
