Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study.
Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study.
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DOI：
10.1186/1476-069x-10-45
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发表时间：
2011-05-21
期刊：
影响因子：
--
通讯作者：
Schwartz J
中科院分区：
文献类型：
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作者：
Wilker EH;Alexeeff SE;Suh H;Vokonas PS;Baccarelli A;Schwartz J
空气颗粒物污染与心血管疾病发病率和死亡率有关，但目前尚不清楚哪些时间窗口和污染物来源是最关键的。MicroRNA（miRNA）被认为参与心血管调节。然而，很少有人知道是否在基因的多态性，处理microRNA影响污染物暴露的反应。我们假设平均时间长于常规测量的一天或两天移动平均值与较高的可溶性细胞间粘附分子-1（sICAM-1）和血管细胞粘附分子-1（sVCAM-1）水平相关，并且固定和移动的来源对这些效应的贡献不同。我们还研究了miRNA加工基因中的单核苷酸多态性（SNP）是否改变了这些关联。从1999年到2008年测量sICAM-1和sVCAM-1，并与细颗粒物（PM2.5）、黑碳和硫酸盐（SO 42-）的空气污染监测相匹配。我们选择了5个miRNA加工基因中的17个SNP。混合效应模型被用来评估污染物的影响，单核苷酸多态性，并在隐性遗传模型下使用重复测量的相互作用。我们的黑碳和PM2.5分析包括723名参与者的1652次观察和1-5次访问。硫酸盐数据可用于672名参与者的1390个观察结果。PM2.5（4.27 μg/m3）7天移动平均值的四分位数变化与sICAM-1和sVCAM-1升高3.1%（95%CI：1.6，4.6）和2.5%（95%CI：0.6，4.5）相关。硫酸盐浓度的四分位距变化（1.39 μg/m3）分别与sICAM-1和sVCAM-1升高1.4%（95%CI：0.04，2.7）和1.6%（95%CI：-0.4，3.7）相关。没有观察到黑碳的显着关联。在与PM2.5的相互作用模型中，rs 1062923纯合子携带者的sICAM-1和sVCAM-1水平均较低。在多重比较调整后，这些相互作用仍然显着。PM2.5七天移动平均值与较高的sICAM-1和sVCAM-1水平相关。SO 4 -2 7天移动平均值与较高的sICAM-1相关，在老年男性中观察到与sVCAM-1的暗示性关联。miRNA加工基因中的SNPs可能会改变环境污染与sICAM-1和sVCAM-1之间的关联，这与动脉粥样硬化和心血管疾病有关。
Particulate air pollution has been associated with cardiovascular morbidity and mortality, but it remains unclear which time windows and pollutant sources are most critical. MicroRNA (miRNA) is thought to be involved in cardiovascular regulation. However, little is known about whether polymorphisms in genes that process microRNAs influence response to pollutant exposure. We hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) levels, and that stationary and mobile sources contribute differently to these effects. We also investigated whether single nucleotide polymorphisms (SNPs) in miRNA-processing genes modify these associations. sICAM-1 and sVCAM-1 were measured from 1999-2008 and matched to air pollution monitoring for fine particulate matter (PM2.5) black carbon, and sulfates (SO42-). We selected 17 SNPs in five miRNA-processing genes. Mixed-effects models were used to assess effects of pollutants, SNPs, and interactions under recessive inheritance models using repeated measures. 723 participants with 1652 observations and 1-5 visits were included in our analyses for black carbon and PM2.5. Sulfate data was available for 672 participants with 1390 observations. An interquartile range change in seven day moving average of PM2.5 (4.27 μg/m3) was associated with 3.1% (95%CI: 1.6, 4.6) and 2.5% (95%CI: 0.6, 4.5) higher sICAM-1 and sVCAM-1. Interquartile range changes in sulfates (1.39 μg/m3) were associated with 1.4% higher (95%CI: 0.04, 2.7) and 1.6% (95%CI: -0.4, 3.7) higher sICAM-1 and sVCAM-1 respectively. No significant associations were observed for black carbon. In interaction models with PM2.5, both sICAM-1 and sVCAM-1 levels were lower in rs1062923 homozygous carriers. These interactions remained significant after multiple comparisons adjustment. PM2.5 seven day moving averages are associated with higher sICAM-1 and sVCAM-1 levels. SO4-2 seven day moving averages are associated with higher sICAM-1 and a suggestive association was observed with sVCAM-1 in aging men. SNPs in miRNA-processing genes may modify associations between ambient pollution and sICAM-1 and sVCAM-1, which are correlates of atherosclerosis and cardiovascular disease.