Platelet-endothelial cell adhesion molecule-1 gene polymorphism and its soluble level are associated with severe coronary artery stenosis in Chinese Singaporean.
OBJECTIVE
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).


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 (> or =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.


CONCLUSIONS
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.
Wei
Heming
H
Johns Hopkins Singapore-National Heart Centre Vascular Biology Program, Singapore.
Fang
Lu
L
Chowdhury
Sanual H
SH
Gong
Nanling
N
Xiong
Zhuowei
Z
Song
Jie
J
Mak
Koon Hou
KH
Wu
Saizhu
S
Koay
Evelyn
E
Sethi
Sunil
S
Lim
Yean Leng
YL
Chatterjee
Subroto
S
D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D044466:Asian People; D001792:Blood Platelets / Q000378:metabolism*; D023921:Coronary Stenosis / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology; D011110:Polymorphism, Genetic; D012846:Singapore; D012995:Solubility
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1