Abstract
Objective
P-selectin (PSEL) and its ligand, P-selectin glycoprotein ligand-1 (PSGL-1), play
key roles in both the inflammatory response and the atherosclerotic process, but there
are conflicting results regarding the affect of PSEL and PSGL-1 gene variation on
risk for cardiovascular and cerebrovascular disease. We tested the association of
four PSEL and two PSGL-1 polymorphisms with incident coronary heart disease (CHD)
and ischemic stroke among 13,875 participants in the prospective Atherosclerosis Risk
in Communities (ARIC) study. We also tested common haplotypes in the PSEL and PSGL-1
genes to assess associations with incident CHD and ischemic stroke.
Methods and results
Incident ischemic stroke and CHD were identified through annual telephone calls and
hospital and death certificate surveillance. Five hundred and twenty-five validated
ischemic stroke and 1654 CHD events were identified. Allele frequencies for all PSEL
and PSGL-1 polymorphisms were markedly different between whites and African Americans;
therefore, all analyses were performed race-specific. Independent analyses showed
the PSEL 290NN genotype to be a significant predictor of CHD in whites (HRR 1.30,
95%CI 1.00–1.70, P = 0.05). PSGL-1 genotypes carrying the 62I allele were significantly protective for
incident CHD (HRR 0.53, 95%CI 0.31–0.92, P = 0.02) and ischemic stroke (HRR 0.73, 95%CI 0.55–0.97, P = 0.03) in African Americans. Haplotype analyses showed the PSEL NNVP haplotype to be
a significant predictor of incident CHD in whites (HRR 2.09, 95%CI 1.23–3.55, P = 0.006). No significant haplotype findings were observed in African Americans.
Conclusions
PSEL S290N, in single polymorphism analysis and in the haplotypic background with
T715P, was associated with increased risk of incident CHD in whites. The PSGL-1 M62I
polymorphism was associated with decreased risk of both incident CHD and stroke in
African Americans. These findings illustrate the complex relationship between genetic
variation and disease in different racial groups.
Keywords
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Article info
Publication history
Published online: April 11, 2007
Accepted:
March 6,
2007
Received in revised form:
February 15,
2007
Received:
January 10,
2007
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
