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(Hypertension. 2007;49:857.)
© 2007 American Heart Association, Inc.

Original Articles

Corin I555(P568) Allele Is Associated With Enhanced Cardiac Hypertrophic Response to Increased Systemic Afterload

J. Eduardo Rame; Mark H. Drazner; Wendy Post; Ronald Peshock; Joao Lima; Richard S. Cooper; Daniel L. Dries

From the Donald W. Reynolds Cardiovascular Clinical Research Center (M.H.D., R.P., D.L.D.), the Division of Cardiology, University of Texas Southwestern Medical Center, Dallas; the Division of Cardiology (J.E.R.), University of California San Francisco; the Cardiovascular Branch (J.E.R.), National Heart Lung and Blood Institute, Bethesda, Md; Donald W. Reynolds Cardiovascular Clinical Research Center (W.P., J.L.), Division of Cardiology, Johns Hopkins University, Baltimore, Md; the Department of Preventive Medicine and Epidemiology (R.S.C.), Loyola University Stritch School of Medicine, Maywood, Ill; and the Cardiovascular Division (D.L.D.), Hospital of the University of Pennsylvania, Philadelphia.

Correspondence to Daniel L. Dries, University of Pennsylvania, Division of Cardiovascular Medicine, 6 Penn Tower, 3400 Spruce St, Philadelphia, PA 19104. E-mail daniel.dries{at}uphs.upenn.edu

Corin activates pro–A-type naturetic peptide and pro–B-type naturetic peptide into biologically active molecules. We recently identified a minor allele in the corin gene defined by 2 highly linked single nucleotide polymorphisms (T555I and Q568P), which was associated with hypertension in blacks. Because of the direct antihypertrophic effects of the natriuretic peptide system, we hypothesized that the minor corin I555(P568) allele would be associated with an enhanced hypertrophic response to pressure overload. The relationship between systolic blood pressure and indexed left ventricular mass, derived from cardiac MRI, was analyzed in the Dallas Heart Study as a function of corin allele status. The Multi-Ethnic Study of Atherosclerosis was used as a validation cohort. All of the analyses were limited to self-identified blacks without treatment for hypertension. In addition, we genotyped 2114 markers highly informative for African ancestry in the Dallas Heart Study and derived a covariate representing African ancestry for multivariate models. In adjusted analysis, the corin I555(P568) allele was an independent predictor of left-ventricular mass in subjects with elevated systolic blood pressure. Linear spline regression analysis confirmed a significant interaction (P=0.002) between the corin I555(P568) allele and systolic blood pressure as a predictor of left ventricular mass in subjects with systolic blood pressure >120 mm Hg, and this nonlinear interaction was replicated in the Multi-Ethnic Study of Atherosclerosis. In the Dallas Heart Study, the corin I555(P568) allele was also associated with an increased odds for prevalent left ventricular hypertrophy in the presence of untreated hypertension. These data suggest that the corin I555(P568) allele represents a cardiac hypertrophy-sensitizing genetic locus in systemic hypertension.

Key Words: hypertension • left ventricular hypertrophy • natriuretic peptides • genetic polymorphisms • left ventricular remodeling

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