Published online before print September 26, 2002, doi: 10.1161/01.ATV.0000038486.48400.E7
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© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Val64Ile Polymorphism in the C-C Chemokine Receptor 2 Is Associated With Reduced Coronary Artery Calcification
From GlaxoSmithKline (A.M.V., E.J.O., N.K.S., A.R., P.H.E.G.), Stevenage, Hertfordshire, UK, and the University of Pennsylvania School of Medicine (M.L.W., W.G., D.J.R.), Philadelphia.
Correspondence to Daniel J. Rader, MD, 654 BRBII/III, 421 Curie Blvd, Philadelphia, PA 19104-6160. E-mail rader{at}mail.med.upenn.edu
Objective— Studies in mice have shown that genetic disruption of monocyte chemotactic protein-1 or its receptor, the C-C chemokine receptor 2 (CCR2), inhibits atherosclerosis, but few data exist in humans to suggest that the monocyte chemotactic protein-1—CCR2 interaction is important in atherogenesis. A common polymorphism in the human CCR2 gene resulting in a substitution of isoleucine for valine (Val64Ile) has been associated with other disease phenotypes in humans.
Methods and Results— A cohort of first-degree relatives of persons with premature coronary artery disease was recruited and quantitatively phenotyped for the extent of CAC, a marker of coronary atherosclerosis, by using electron beam CT. The extent of CAC was significantly lower in subjects with the CCR2-Ile64 variant (Val/Ile and Ile/Ile genotypes) than in subjects carrying 2 Val64 alleles, even after adjustment for traditional risk factors.
Conclusions— This study provides genetic evidence linking CCR2 with coronary atherosclerosis in humans.
Key Words: atherosclerosis • chemokines • coronary artery calcification • polymorphism • coronary heart disease
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