血小板内皮细胞黏附分子-1（PECAM-1）基因Leu125Val多态性及PECAM-1可溶性水平与亚洲印度人冠状动脉疾病的关联

Association of Leu125Val polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene & soluble level of PECAM-1 with coronary artery disease in Asian Indians.

作者信息

Fang Lu, Wei Heming, Chowdhury Sanual H, Gong Nanling, Song Jie, Heng Chew Kiat, Sethi Sunil, Koh Tian Hai, Chatterjee Subroto

机构信息

Johns Hopkins Singapore-National Heart Centre Vascular Biology Program, National University of Singapore.

出版信息

Indian J Med Res. 2005 Feb;121(2):92-9.

PMID:15756041

Abstract

BACKGROUND & OBJECTIVES: Platelet endothelial cell adhesion molecule-1 (PECAM-1) plays a key role in the transendothelial migration of circulating leukocytes (diapedesis) during vascular inflammation. We hypothesized that genetic variation and the level of soluble PECAM-1 could be associated with the development of atherosclerosis and conducted a study on gene polymorphisms of PECAM-1 and soluble PECAM-1 levels in Asian Indian patients with coronary artery disease (CAD) in Singapore.

METHODS

Of the 137 angiographically confirmed patients (> or =70% stenosis) of CAD and 110 controls in Asian Indian population, two single nucleotide polymorphisms (SNPs) of PECAM-1 gene, C+373G (Leu125Val) at exon 3 and G+1688A (Ser563Asn) at exon 8 were analyzed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) strategy. In addition, plasma soluble PECAM-1, P-selection and lipid profile were measured. Chi- square test and student t test were adopted to compare categorical and continuous variables, respectively.

RESULTS

A significant decrease in C allele frequency but increase in G allele frequency of the Leu125Val (C/G) polymorphism were observed in CAD patients as compared with controls (0.54/0.46 vs 0.663/0.337 respectively, P=0.008). Alteration in genotype distributions (CC, CG and GG) of the Leu125Val polymorphism between CAD patients and controls (P=0.009) was also significant. A similar trend was observed on the allele frequencies (G/A) and genotype distributions of Ser563Asn (G/A) polymorphism, though the difference did not reach significance. On the other hand, plasma level of soluble PECAM-1 (sPECAM-1) was markedly elevated in CAD patients (P=0.006), and associated with soluble P-selectin and lipid profiles.

INTERPRETATION & CONCLUSION: Our study showed that Leu125Val polymorphism of PECAM-1 gene and elevated soluble PECAM-1 were related to severe coronary artery stenosis in CAD patients of Asian Indian origin in Singapore. Our data also suggest that PECAM-1 plays an important role in the development of atherosclerosis.

摘要

背景与目的

血小板内皮细胞黏附分子-1（PECAM-1）在血管炎症期间循环白细胞的跨内皮迁移（渗出）中起关键作用。我们推测基因变异和可溶性PECAM-1水平可能与动脉粥样硬化的发生有关，并对新加坡亚裔印度裔冠心病（CAD）患者的PECAM-1基因多态性和可溶性PECAM-1水平进行了研究。

方法

在亚裔印度人群中，对137例经血管造影证实的CAD患者（狭窄≥70%）和110例对照者，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）策略分析PECAM-1基因的两个单核苷酸多态性（SNP），即外显子3的C+373G（Leu125Val）和外显子8的G+1688A（Ser563Asn）。此外，检测血浆可溶性PECAM-1、P-选择素和血脂谱。分别采用卡方检验和学生t检验比较分类变量和连续变量。

结果

与对照组相比，CAD患者Leu125Val（C/G）多态性的C等位基因频率显著降低，G等位基因频率升高（分别为0.54/0.46和0.663/0.337，P=0.008）。CAD患者和对照组之间Leu125Val多态性的基因型分布（CC、CG和GG）改变也有显著性差异（P=0.009）。Ser563Asn（G/A）多态性的等位基因频率（G/A）和基因型分布也观察到类似趋势，尽管差异未达到显著性。另一方面，CAD患者血浆可溶性PECAM-1（sPECAM-1）水平显著升高（P=0.006），且与可溶性P-选择素和血脂谱相关。