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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1549.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Soluble P-Selectin, SELP Polymorphisms, and Atherosclerotic Risk in European-American and African-African Young Adults

The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Alexander P. Reiner; Christopher S. Carlson; Bharat Thyagarajan; Mark J. Rieder; Joseph F. Polak; David S. Siscovick; Deborah A. Nickerson; David R. Jacobs, Jr; Myron D. Gross

From the Departments of Epidemiology (A.P.R., D.S.S.) and Genome Sciences (M.J.R., D.A.N.), University of Washington, Seattle; the Division of Public Health Sciences (C.S.C.), Fred Hutchinson Cancer Research Center, Seattle, Wash; the Department of Laboratory Medicine and Pathology (B.T., M.D.G.) and the Division of Epidemiology, School of Public Health (D.R.J., M.D.G.), University of Minnesota, Minneapolis; and the Department of Radiology (J.F.P.), Tufts-New England Medical Center, Boston, Mass.

Correspondence to Alex Reiner, University of Washington, Department of Genome Sciences, Box 357236, Seattle, WA 98195. E-mail apreiner{at}u.washington.edu

Abstract

Objective— To characterize the genetic and clinical correlates of soluble P-selectin, and the relationship of P-selectin to atherosclerotic risk, in young European-American (EA) and African-American (AA) adults.

Methods and Results— We assessed the interrelationships between 25 common SELP polymorphisms, soluble P-selectin, and atherosclerotic risk in 1222 EA and 1072 AA from the longitudinal population-based CARDIA study. Male sex, smoking, blood pressure, and metabolic status were strong cross-sectional correlates of soluble P-selectin among CARDIA subjects aged 33 to 45 years, explaining 13% of the variance. Among EAs, higher soluble P-selectin predicted carotid intima-media thickness (IMT) measured 5 years later, even after accounting for traditional risk factors. Common SELP nucleotide sequence variants explained 11% and 5% of the interindividual variation in soluble P-selectin levels in EAs and AAs, respectively. Four distinct variants contributed to P-selectin phenotype in EAs, including a polymorphism of the 5' SELP haplotype block associated with carotid IMT. Half of the phenotypic variation attributable to SELP in EAs could be explained by the Thr715Pro polymorphism, whereas Val599Leu was more strongly associated with soluble P-selectin among AAs.

Conclusions— Common SELP polymorphisms were associated with soluble P-selectin and carotid IMT in young adults, but the patterns of association differed between EAs and AAs. These results support the role of P-selectin in the preclinical stages of atherosclerosis.

Common SELP polymorphisms were associated with soluble P-selectin and carotid wall thickness in young adults, but the patterns of association differed between European-Americans and African-Americans. These results support the role of P-selectin in the preclinical stages of atherosclerosis.

Key Words: P-selectin • carotid atherosclerosis • haplotype