慢性呼吸道疾病候选基因与接触颗粒物之间相互作用所导致的血压体位变化。
Postural changes in blood pressure associated with interactions between candidate genes for chronic respiratory diseases and exposure to particulate matter.
作者信息
Wilker Elissa, Mittleman Murray A, Litonjua Augusto A, Poon Audrey, Baccarelli Andrea, Suh Helen, Wright Robert O, Sparrow David, Vokonas Pantel, Schwartz Joel
机构信息
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA.
出版信息
Environ Health Perspect. 2009 Jun;117(6):935-40. doi: 10.1289/ehp.0800279. Epub 2009 Feb 3.
BACKGROUND
Fine particulate matter [aerodynamic diameter </= 2.5 mum (PM(2.5))] has been associated with autonomic dysregulation.
OBJECTIVE
We hypothesized that PM(2.5) influences postural changes in systolic blood pressure (DeltaSBP) and in diastolic blood pressure (DeltaDBP) and that this effect is modified by genes thought to be related to chronic lung disease.
METHODS
We measured blood pressure in participants every 3-5 years. DeltaSBP and DeltaDBP were calculated as sitting minus standing SBP and DBP. We averaged PM(2.5) over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP x PM(2.5) interactions on DeltaSBP and DeltaDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors.
RESULTS
Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater DeltaDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater DeltaSBP. Because SNPs associated with DeltaSBP in our analysis are in genes along the renin-angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM(2.5).
CONCLUSIONS
PM(2.5) influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.
背景
细颗粒物[空气动力学直径≤2.5微米（PM2.5）]与自主神经调节异常有关。
目的
我们假设PM2.5会影响收缩压（ΔSBP）和舒张压（ΔDBP）的体位变化，并且这种效应会被认为与慢性肺病相关的基因所改变。
方法
我们每3至5年测量一次参与者的血压。ΔSBP和ΔDBP通过坐位收缩压和舒张压减去站立位收缩压和舒张压来计算。我们在研究访视前48小时内对PM2.5进行平均，并分析了25个基因中的202个单核苷酸多态性（SNP）。为解决多重比较问题，数据被分层到一个拆分样本中。在发现队列中，使用具有个体特异性随机截距的混合模型分析SNP×PM2.5相互作用对ΔSBP和ΔDBP的影响。我们将相互作用的阳性结果定义为p<0.1；我们仅在重复队列中分析这些SNP，如果p<0.025且符号相同则予以确认。在根据人体测量和生活方式因素进行调整的模型中，在整个队列中分析已确认的关联。
结果
945名参与者纳入我们的分析。PHD指蛋白11（PHF11）中rs9568232的一种相互作用与更大的ΔDBP相关。基质金属蛋白酶1（MMP1）中的rs1144393以及2型肌醇1,4,五磷酸受体（ITPR2）中的rs16930692、rs7955200和rs10771283的相互作用与显著更大的ΔSBP相关。由于我们分析中与ΔSBP相关的SNP位于肾素 - 血管紧张素途径沿线的基因中，我们随后检查了影响该途径的药物，并观察到血管紧张素受体阻滞剂与PM2.5存在显著相互作用，而血管紧张素转换酶抑制剂则没有。
结论
PM2.5影响血压和自主神经功能。这种效应会被同样作用于该途径的基因和药物所改变。
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