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.
OBJECTIVE
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.


CONCLUSIONS
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.
Fang
Lu
L
Johns Hopkins Singapore-National Heart Centre Vascular Biology Program, National University of Singapore.
Wei
Heming
H
Chowdhury
Sanual H
SH
Gong
Nanling
N
Song
Jie
J
Heng
Chew Kiat
CK
Sethi
Sunil
S
Koh
Tian Hai
TH
Chatterjee
Subroto
S
D001483:Base Sequence; D003324:Coronary Artery Disease / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D007194:India; D007930:Leucine / Q000235:genetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic; D012995:Solubility; D014633:Valine / Q000235:genetics*
D017931:DNA Primers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D007930:Leucine; D014633:Valine