National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC, USA.
Hum Genet. 2019 Jun;138(6):547-561. doi: 10.1007/s00439-019-02004-w. Epub 2019 Apr 9.
Air pollution is recognized as causal factor for cardiovascular disease (CVD) and is associated with multiple CVD risk factors. Substantial research effort has been invested in understanding the linkages between genetic variation and CVD risk, resulting in over 50 CVD-associated genetic loci. More recently, gene-air pollution interaction studies have quantified the contribution of genetic variation to inter-individual heterogeneity in air pollution health risks, and aided in elucidating mechanisms of air pollution exposure health risks. Here, we perform a comprehensive review of gene-air pollution interaction studies for CVD, as well as risk factors and emerging CVD biomarkers. The literature review revealed that most published interaction studies have been candidate gene studies, causing observed interactions to cluster in a few genes related to detoxification (GSTM1 and GSTT1), inflammation (IL-6), iron processing (HFE), and microRNA processing (GEMIN4 and DGCR8). There have been a few genome-wide interaction studies with results indicating that interactions extend beyond commonly considered genetic loci. Gene-air pollution interactions are observed for exposure periods ranging from hours to years and a variety of air pollutants including particulate matter, gaseous pollutants, and pollutant sources such as traffic. Though the existing evidence for the existence of relevant gene-air pollution interactions for CVD outcomes is substantial, it could be strengthened by improved replication and meta-analyses as well as functional validation.
空气污染被认为是心血管疾病 (CVD) 的致病因素，与多种 CVD 风险因素有关。大量的研究工作致力于理解遗传变异与 CVD 风险之间的联系，已经确定了 50 多个与 CVD 相关的遗传位点。最近，基因-空气污染相互作用研究已经量化了遗传变异对个体间空气污染健康风险差异的贡献，并有助于阐明空气污染暴露健康风险的机制。在这里，我们对 CVD 以及风险因素和新兴 CVD 生物标志物的基因-空气污染相互作用研究进行了全面综述。文献综述表明，大多数已发表的相互作用研究都是候选基因研究，导致观察到的相互作用集中在少数与解毒（GSTM1 和 GSTT1）、炎症（IL-6）、铁处理（HFE）和 microRNA 处理（GEMIN4 和 DGCR8）相关的基因中。也有一些全基因组相互作用研究的结果表明，相互作用不仅限于通常考虑的遗传位点。已经观察到基因-空气污染相互作用的暴露时间从几小时到几年不等，涉及的空气污染物包括颗粒物、气态污染物以及交通等污染源。尽管现有证据表明基因-空气污染相互作用与 CVD 结局有关，但通过改进复制和荟萃分析以及功能验证，可以进一步加强这一证据。
