Specific P-selectin and P-selectin glycoprotein ligand-1 genotypes/haplotypes are associated with risk of incident CHD and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.
Specific P-selectin and P-selectin glycoprotein ligand-1 genotypes/haplotypes are associated with risk of incident CHD and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.
复制标题
DOI：
10.1016/j.atherosclerosis.2007.03.007
复制
发表时间：
2007-11-01
期刊：
影响因子：
5.3
通讯作者：
Boerwinkle, Eric
中科院分区：
文献类型：
--
作者：
Volcik, Kelly A;Ballantyne, Christie M;Boerwinkle, Eric
目的：P-selectin（PSEL）及其配体P-selectin glycoprotein ligand-1（PSGL-1）在炎症反应和动脉粥样硬化过程中起着关键作用，但PSEL和PSGL-1基因变异对心脑血管疾病风险的影响存在着相互矛盾的结果。我们在前瞻性社区动脉粥样硬化风险（ARIC）研究的13，875名参与者中检测了4种PSEL和2种PSGL-1多态性与冠心病（CHD）和缺血性卒中的相关性。我们还测试了常见的单倍型PSEL和PSGL-1基因，以评估与冠心病和缺血性stroke.METHODS和RESULTS：事件缺血性中风和冠心病确定通过每年的电话和医院和死亡证明监测。确定了525例经验证的缺血性卒中和1654例CHD事件。所有PSEL和PSGL-1多态性的等位基因频率在白人和非洲裔美国人之间存在显著差异;因此，所有分析都是种族特异性的。独立分析显示PSEL 290 NN基因型是白人CHD的显著预测因子（HRR 1.30，95%CI 1.00-1.70，P=0.05）。在非裔美国人中，携带62 I等位基因的PSGL-1基因型对冠心病（HRR 0.53，95%CI 0.31-0.92，P=0.02）和缺血性卒中（HRR 0.73，95%CI 0.55-0.97，P=0.03）的发生具有显著保护作用。单倍型分析显示PSEL NNVP单倍型是白人CHD事件的显著预测因子（HRR 2.09，95%CI 1.23-3.55，P=0.006）。在AfricanAmerican.CONCLUSIONS：PSEL S290 N，在单一多态性分析和单倍型背景与T715 P，与白人冠心病事件的风险增加。PSGL-1 M62 I多态性与非裔美国人CHD和卒中发病风险降低相关。这些发现说明了不同种族群体中遗传变异和疾病之间的复杂关系。
OBJECTIVE: P-selectin (PSEL) and its ligand, P-selectin glycoprotein ligand-1 (PSGL-1), play key roles in both the inflammatory response and the atherosclerotic process, but there are conflicting results regarding the affect of PSEL and PSGL-1 gene variation on risk for cardiovascular and cerebrovascular disease. We tested the association of four PSEL and two PSGL-1 polymorphisms with incident coronary heart disease (CHD) and ischemic stroke among 13,875 participants in the prospective Atherosclerosis Risk in Communities (ARIC) study. We also tested common haplotypes in the PSEL and PSGL-1 genes to assess associations with incident CHD and ischemic stroke.METHODS AND RESULTS: Incident ischemic stroke and CHD were identified through annual telephone calls and hospital and death certificate surveillance. Five hundred and twenty-five validated ischemic stroke and 1654 CHD events were identified. Allele frequencies for all PSEL and PSGL-1 polymorphisms were markedly different between whites and African Americans; therefore, all analyses were performed race-specific. Independent analyses showed the PSEL 290NN genotype to be a significant predictor of CHD in whites (HRR 1.30, 95%CI 1.00-1.70, P=0.05). PSGL-1 genotypes carrying the 62I allele were significantly protective for incident CHD (HRR 0.53, 95%CI 0.31-0.92, P=0.02) and ischemic stroke (HRR 0.73, 95%CI 0.55-0.97, P=0.03) in African Americans. Haplotype analyses showed the PSEL NNVP haplotype to be a significant predictor of incident CHD in whites (HRR 2.09, 95%CI 1.23-3.55, P=0.006). No significant haplotype findings were observed in African Americans.CONCLUSIONS: PSEL S290N, in single polymorphism analysis and in the haplotypic background with T715P, was associated with increased risk of incident CHD in whites. The PSGL-1 M62I polymorphism was associated with decreased risk of both incident CHD and stroke in African Americans. These findings illustrate the complex relationship between genetic variation and disease in different racial groups.