P-selectin Thr715Pro polymorphism predicts P-selectin levels but not risk of incident coronary heart disease or ischemic stroke in a cohort of 14595 participants: The Atherosclerosis Risk In Communities Study

Volcik, Kelly A.; Ballantyne, Christie M.; Coresh, Josef; Folsom, Aaron R.; Wu, Kenneth K.; Boerwinkle, Eric

doi:10.1016/j.atherosclerosis.2005.07.010

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Volume 186, Issue 1 , Pages 74-79, May 2006

P-selectin Thr715Pro polymorphism predicts P-selectin levels but not risk of incident coronary heart disease or ischemic stroke in a cohort of 14595 participants: The Atherosclerosis Risk In Communities Study

Kelly A. Volcik
- Human Genetics Center, University of Texas Houston Health Science Center, 1200 Herman Pressler Dr., Houston, TX 77030, USA
Christie M. Ballantyne
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
Josef Coresh
- Department of Epidemiology, John Hopkins University, Baltimore, MD, USA
Aaron R. Folsom
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA
Kenneth K. Wu
- Department of Hematology, University of Texas Health Science Center, Houston, TX, USA
Eric Boerwinkle
- Human Genetics Center, University of Texas Houston Health Science Center, 1200 Herman Pressler Dr., Houston, TX 77030, USA
- Corresponding author. Tel.: +1 713 500 9800; fax: +1 713 500 0900.

Received 5 April 2005; received in revised form 30 June 2005; accepted 8 July 2005. published online 30 August 2005.

Abstract

Objective

Inflammation, characterized by the recruitment/adhesion of circulating leukocytes by cellular adhesion molecules, plays an important role in the pathogenesis of atherosclerosis. Genetic analyses of P-selectin, a key adhesion molecule in the progression of atherosclerosis, have provided conflicting results regarding the role of variation within the P-selectin gene and risk for heart disease. No studies have examined the association of this polymorphism with stroke. Therefore, we examined the association of the P-selectin Thr715Pro polymorphism with incident coronary heart disease (CHD) and ischemic stroke among 14595 participants in the prospective cohort of the Atherosclerosis Risk in Communities (ARIC) Study.

Methods and results

Incidences of ischemic stroke and CHD were determined through annual telephone calls and hospital and death certificate surveillance. Four hundred fifty-six validated ischemic stroke and 1533 CHD events were identified. P-selectin Pro715 allele frequency was determined in whites and African–Americans, respectively, for CHD cases (0.11, 0.02), CHD non-cases (0.11, 0.02), ischemic stroke cases (0.11, 0.02) and stroke non-cases (0.11, 0.02). The P-selectin Pro715 allele was not associated with risk of CHD or stroke in whites or African–Americans. P-selectin levels, however, were associated with the P-selectin Thr715Pro variant in whites, but not in African–Americans.

Conclusions

Genotypes carrying the P-selectin Pro715 variant allele are associated with decreased P-selectin levels compared to the homozygous wild-type genotype in whites. The P-selectin Thr715Pro polymorphism is not associated with incident CHD or ischemic stroke in either whites or African–Americans.

Keywords: Cell adhesion molecules, Coronary heart disease, Stroke, P-selectin, Association