Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke
Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke
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DOI：
10.1038/ejhg.2009.42
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发表时间：
2009-10-01
影响因子：
5.2
通讯作者：
Goris, An
中科院分区：
文献类型：
--
作者：
Lemmens, Robin;Abboud, Sherine;Goris, An
最近，全基因组分析显示染色体9 p21上的变异与心肌梗死相关。我们调查了这种关联是否也存在于比利时冠状动脉疾病（CAD）患者人群中。由于CAD和缺血性脑血管病（CVD）被认为有一些共同的致病途径，我们进一步研究了9 p21与这种疾病的关系。在CAREGENE研究的926例CAD患者、鲁汶卒中遗传学研究（LSGS）和比利时卒中研究（BSS）的648例CVD患者以及828例无关对照中，对9号染色体上的SNP rs 10757278进行基因分型。对这两种血管疾病进行了系统综述和荟萃分析。危险等位基因rs 10757278 *G的频率在CAD病例中为55%，对照组为48%，比值比（OR）为1.35（1.18-1.54），P = 1.3 x 10（-5）。未发现与CVD相关，OR 1.03（0.89-1.19），P = 0.73。Meta分析显示，风险变量与CAD之间存在一致的关系。然而，在CVD中使用Meta分析方法，仅观察到边缘相关性，在排除有CAD病史的患者后不再存在。9号染色体上的风险变异，标记为rs 10757278，与比利时人群中的冠心病相关，但与孤立的CVD无关。这些发现表明CAD与CVD的致病机制不同。European Journal of Human Genetics（2009）17，1287-1293; doi：10.1038/ejhg.2009.42; 2009年3月25日在线发表
Recently, genome-wide analyses revealed that variants on chromosome 9p21 are associated with myocardial infarction. We investigated whether this association was also present in a Belgian population of coronary artery disease (CAD) patients. As CAD and ischemic cerebrovascular disease (CVD) are thought to share some pathogenic pathways, we further examined the association of 9p21 with this disease. SNP rs10757278 on chromosome 9 was genotyped in 926 patients with CAD from the CAREGENE study, in 648 patients with CVD from the Leuven Stroke Genetics Study (LSGS) and the Belgian Stroke Study (BSS) and in 828 unrelated controls. A systematic review and meta-analysis were carried out in both vascular diseases. The frequency of the risk allele, rs10757278*G, was 55% in CAD cases versus 48% in controls, odds ratio (OR) 1.35 (1.18-1.54), P = 1.3 x 10(-5). No association was found with CVD, OR 1.03 (0.89-1.19), P = 0.73. Meta-analysis revealed a consistent relationship between the risk variant and CAD. However, using a meta- analytic approach in CVD, only a marginal association was observed, which was no longer present after excluding patients with a history of CAD. The risk variant on chromosome 9, tagged by rs10757278, is associated with coronary heart disease in the Belgian population, but not with isolated CVD. These findings suggest different pathogenic mechanisms in CAD versus CVD. European Journal of Human Genetics (2009) 17, 1287-1293; doi: 10.1038/ejhg.2009.42; published online 25 March 2009