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.

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.

Ethnic variations of a retinoblastoma susceptibility gene (RB1) polymorphism in eight Asian populations.

An A --> G single nucleotide polymorphism (SNP) at nucleotide 153,104 in the retinoblastoma susceptibility locus (RB1) at 13q14 was previously reported to be present only in Asians. In this study, we determined the distribution of this SNP in normal Southeast Asian populations (Chinese, Malay, Javanese, Thai, Filipino), in South Asian populations (Bangladeshi, Pakistani Pushtun and Indian) and in Chinese retinoblastoma cases and control subjects. The RB1 SNP was present in all populations at an overall frequency of =/< 0.18. Heterozygosity was higher in the Southeast Asian groups (0.14-0.34) than in the South Asian groups (Bangladeshi and Indian) (0.04-0.06). Significant differences in allele frequencies were found between the two population groups. Interestingly, our Pakistani population comprised of ethnic Pushtuns from northwest Pakistan was significantly different from the neighbouring Bangladeshi and Indian populations. No significant difference was found between Chinese case patients and control subjects. This RB1 SNP appears to be an ethnic variant prevalent in Southeast Asian populations and may be useful for studying RB1 inheritance by pedigree analysis.