血小板内皮细胞黏附分子-1基因多态性与急性心肌梗死的相关性研究

目的 研究血小板内皮细胞黏附分子-1(PECAM-1)基因单核昔酸多态性及其单倍型与急性心肌梗死(AMI)易感性之间的关系;同时分析PECAM-1基因型及血清水平与AMI的相关性.方法 以180例AMI患者和200例健康对照者为研究对象,应用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)和DNA测序的方法 对PECAM-1基因Leu125Val、Asn563Ser和Gly670Arg单苷酸多态性进行基因分型,同时采用酶联免疫吸附法检测血清PECAM-1水平.用SHEsis软件分析PECAM-1基因的连锁不平衡及单倍型频率.结果 PECAM-1基因Asn563Ser和Gly670Arg多态性在AMI患者和正常人群中分布差异无统计学意义(P>0.05),而PECAM-1基因Leu125Val多态性在两组人群中的分布差异存在统计学意义(P<0.05).等位基因频率的相对风险分析发现,Val等位基因携带者患AMI的风险是Leu等位基因的1.480倍[比值比(OR)=1.480,95%可信区间(CI)为1.111～1.972,P=0.007];携带Val等位基因的AMI患者血清PECAM-1水平显著高于不携带者(P<0.01).联合基因型分析发现,PECAM-1基因Leu125Val、Asn563Ser和Gly670Arg单核苷酸多态性存在着强烈的连锁不平衡,与对照组比较,Val-Ser-Arg基因单倍型携带者显著增加了AMI的发病风险(OR=1.489,95%CI为1.118～1.984,P=0.006).结论 PECAM-1基因Leu125Val多态性和Val-Ser-Arg单倍型与AMI的发病具有相关性,其中Val等位基因可能足AMI的遗传易感基因,携带Val等位基因的个体可能通过促进PECAM-1的高度表达进而增加了AMI的发病风险.

Study of association of platelet endothelial cell adhesion molecule-I gene polymorphism with acute myocardial infarction

Objective To investigate the association of single nucleotide polymorphism (SNP) and its haplotypes of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with susceptibility to acute myocardial infarction (AMI), and to analyze association the serum levels and genotypes of PECAM-1 with AMI. Methods Three SNPs of PECAM-1 gene Leu125Val, Asn563Ser and Gly670Arg were analyzed in 180 patients with AMI and 200 age and sex matched controls, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy, and the serum level of PECAM-1 was determined by enzyme linked immunosorbent assay (ELISA). Frequency of haplotypes and linkage disequilibrium of PECAM-1 gene in different groups were analyzed by SHEsis programs. Results The distributions of PECAM-1 gene Asn563Ser and Gly670Arg polymorphisms were not different between AMI and control group (P>0. 05), but the PECAM- 1 gene Leu 125Val polymorphism was significantly different (P<0. 05). The relative risk suffered from AMI of Val allele was 1. 480 folds of the Leu allele carriers [odds ratio (OR) = 1. 480, 95% confidence interval (CI) : 1. 111 - 1. 972, P=0. 007]; the serum level of PECAM-1 Val allele carriers was significantly higher than that of noncarriers (P<0. 01). With the results of the genotyping analyses, PECAM-1 gene Leu125Val, Asn563Ser and Gly670Arg polymorphisms showed strong linkage disequilibrium, and the Val-Ser-Arg haplotype was associated with a significantly increased risk of AMI as compared with the controls (OR=1. 489, 95%CI: 1. 118 - 1. 984, P=0. 006). Conclusion PECAM-1 gene Leu125Val polymorphism and its Val-Ser-Arg haplotype are associated with AMI, Val allele is an important genetic susceptibility gene for AMI. The PECAM-1 Val allele carriers may have a higher risk by enhancing the PECAM-1 expression in the pathogenesis of AMI.