Author/Authors :
Heming Wei، نويسنده , , Lu Fang، نويسنده , , Sanual H. Chowdhury، نويسنده , , Nanling Gong، نويسنده , , Zhuowei Xiong، نويسنده , , Xian-Jie Song، نويسنده , , Koon Hou Mak، نويسنده , , Saizhu Wu، نويسنده , , Evelyn Koay، نويسنده , , Sunil Sethi، نويسنده , , Yean Leng Lim، نويسنده , , Subroto Chatterjee، نويسنده ,
Abstract :
Objectives:
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) mediates the transendothelial migration of circulating leukocytes, a characteristic change in vascular inflammation leading to atherosclerotic plaque development. We hypothesized that genetic variation and soluble level of PECAM-1 could be associated with coronary artery disease (CAD).
Design and methods:
We analyzed two single nucleotide polymorphisms (SNPs) of PECAM-1 gene C+373G (Leu125Val) at exon 3, which encodes the first extracellular (Ig)-like domain that mediates the homophilic binding of PECAM-1, and G+1688A (Ser563Asn) at exon 8 in 144 angiographically documented (≥70% stenosis) patients with CAD and 150 age- and sex-matched controls in the Chinese population in Singapore, using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) strategy. Level of plasma soluble PECAM-1 (sPECAM-1) was measured by ELISA.
Results:
The Leu125Val polymorphism was associated with CAD (P< 0.01). Also, the level of sPECAM-1 is was found to be elevated in CAD patients (P = 0.005). Moreover, subjects with the homozygous GG genotype of the Leu125Val polymorphism had higher sPECAM-1 levels (P = 0.005). The level of sPECAM-1 was further correlated to soluble platelet selectin (sP-selectin, also measured by ELISA), platelet count, and total white blood cell count (WBC), suggesting that platelets are a major source of sPECAM-1 and platelet activation and inflammation may contribute to PECAM-1 elevations in CAD patients.
Conclusion:
The Leu125Val polymorphism of PECAM-1 and the level of sPECAM-1 are associated with CAD in Chinese in Singapore. The level of sPECAM-1 is also associated with platelet activation and inflammation and correlated to the Leu125Val polymorphism. Our data suggest that PECAM-1 plays an important role in the development of atherosclerosis.
Keywords :
atherosclerosis , coronary artery disease , gene polymorphism , PECAM-1