Published Online
on October 10, 2005

A more recent version of this article appeared on October 18, 2005

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Submitted on December 12, 2004
Revised on July 21, 2005
Accepted on July 25, 2005

Corin Gene Minor Allele Defined by 2 Missense Mutations Is Common in Blacks and Associated With High Blood Pressure and Hypertension

Daniel L. Dries MD, MPH^*, Ronald G. Victor MD, J. Eduardo Rame MD, MPhil, Richard S. Cooper MD, Xiaodong Wu PhD, Xiaofeng Zhu PhD, David Leonard PhD, Su-Inn Ho MA, Qingyu Wu MD, PhD, Wendy Post MD, and Mark H. Drazner MD, MSc

From the Donald W. Reynolds Cardiovascular Clinical Research Center (D.L.D., R.V., D.L., S.-I.H., M.H.D.), Division of Cardiology (D.L.D., M.H.D.), and Hypertension Division (R.V., D.L.), University of Texas at Southwestern Medical Center, Dallas; Department of Preventive Medicine and Epidemiology, Loyola University Stritch School of Medicine, Maywood, Ill (R.S.C., X.W., X.Z.); Cardiovascular Branch, National Heart, Lung and Blood Institute, Bethesda, Md (J.E.R.); Division of Cardiology (J.E.R., W.P.) and Donald W. Reynolds Cardiovascular Clinical Research Center (W.P.), Johns Hopkins Hospital, Baltimore, Md: and Department of Cardiovascular Research, Berlex Biosciences, Richmond, Calif (Q.W.).

^* To whom correspondence should be addressed. E-mail: daniel.dries{at}uphs.upenn.edu.

Background--The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes.

Method and Results--This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in 12% of blacks but was extremely rare in whites (<0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension (odds ratio, 1.63; 95% CI, 1.11 to 2.38; P=0.013). The corin I555 (P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7±20.7 versus 129.4±17.4 mm Hg; P=0.029) and adjusted (132.5±1.6 versus 128.9±0.6 mm Hg; P=0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis (odds ratio, 1.50; 95% CI, 1.09 to 2.06; P=0.014). In addition, the association of the minor corin I555 (P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8±1.9 versus 121.4±0.7 mm Hg; P=0.03).

Conclusions--The corin I555 (P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension.

Key words: atrial natriuretic factor • genes • genetics • hypertension • peptides

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