Patel Riyaz S, Asselbergs Folkert W, Quyyumi Arshed A, Palmer Tom M, Finan Chris I, Tragante Vinicius, Deanfield John, Hemingway Harry, Hingorani Aroon D, Holmes Michael V
Department of Epidemiology and Public Health, University College London, London, United Kingdom; Department of Cardiology, The Heart Hospital, University College London NHS Trust, London, United Kingdom; Genetic Epidemiology Group, Department of Epidemiology and Public Health, Institute of Cardiovascular Science, University College London, London, United Kingdom.
Genetic Epidemiology Group, Department of Epidemiology and Public Health, Institute of Cardiovascular Science, University College London, London, United Kingdom; Department of Cardiology, Division of Heart & Lungs, University Medical Center, Utrecht, the Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands.
J Am Coll Cardiol. 2014 Jun 3;63(21):2234-45. doi: 10.1016/j.jacc.2014.01.065. Epub 2014 Mar 7.
The purpose of this analysis was to compare the association between variants at the chromosome 9p21 locus (Ch9p21) and risk of first versus subsequent coronary heart disease (CHD) events through systematic review and meta-analysis.
Ch9p21 is a recognized risk factor for a first CHD event. However, its association with risk of subsequent events in patients with established CHD is less clear.
We searched PubMed and EMBASE for prospective studies reporting association of Ch9p21 with incident CHD events and extracted information on cohort type (individuals without prior CHD or individuals with established CHD) and effect estimates for risk of events.
We identified 31 cohorts reporting on 193,372 individuals. Among the 16 cohorts of individuals without prior CHD (n = 168,209), there were 15,664 first CHD events. Ch9p21 was associated with a pooled hazard ratio (HR) of a first event of 1.19 (95% confidence interval: 1.17 to 1.22) per risk allele. In individuals with established CHD (n = 25,163), there were 4,436 subsequent events providing >99% and 91% power to detect a per-allele HR of 1.19 or 1.10, respectively. The pooled HR for subsequent events was 1.01 (95% confidence interval: 0.97 to 1.06) per risk allele. There was strong evidence of heterogeneity between the effect estimates for first and subsequent events (p value for heterogeneity = 5.6 × 10(-11)). We found no evidence for biases to account for these findings.
Ch9p21 shows differential association with risk of first versus subsequent CHD events. This has implications for genetic risk prediction in patients with established CHD and for mechanistic understanding of how Ch9p21 influences risk of CHD.
本分析旨在通过系统评价和荟萃分析，比较9号染色体p21位点（Ch9p21）的变异与首次及后续冠心病（CHD）事件风险之间的关联。
Ch9p21是首次发生CHD事件的公认风险因素。然而，其与已确诊CHD患者后续事件风险的关联尚不清楚。
我们检索了PubMed和EMBASE，以查找报告Ch9p21与CHD事件发生关联的前瞻性研究，并提取了队列类型（无既往CHD的个体或已确诊CHD的个体）以及事件风险的效应估计值等信息。
我们识别出31个队列，涉及193,372名个体。在16个无既往CHD的个体队列（n = 168,209）中，有15,664例首次CHD事件。Ch9p21与每风险等位基因首次事件的合并风险比（HR）为1.19（95%置信区间：1.17至1.22）。在已确诊CHD的个体（n = 25,163）中，有4,436例后续事件，分别提供了>99%和91%的检验效能以检测每等位基因HR为1.19或1.10。每风险等位基因后续事件的合并HR为1.01（95%置信区间：0.97至1.06）。首次和后续事件的效应估计值之间存在异质性的有力证据（异质性p值 = 5.6 × 10(-11)）。我们未发现能解释这些结果的偏倚证据。
Ch9p21与首次及后续CHD事件风险的关联存在差异。这对已确诊CHD患者的遗传风险预测以及对Ch9p21如何影响CHD风险的机制理解具有重要意义。
