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.

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.