on September 26, 2002
Published online before print September 26, 2002, doi: 10.1161/01.ATV.0000038486.48400.E7
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Submitted on April 5, 2002
Accepted on August 26, 2002
Val64Ile Polymorphism in CCR2 Is Associated With Reduced Coronary Artery Calcification
Ana M. Valdes ;
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.
* To whom correspondence should be addressed. E-mail: rader{at}mail.med.upenn.edu.
Objective—A Val64Ile polymorphism in CCR2 was studied for its association with coronary artery calcification (CAC). The extent of CAC was lower in carriers of the Ile64 variant than in subjects with 2 Val64 alleles, and this was independent of traditional risk factors, suggesting that genetic variation in CCR2 may influence atherogenesis. Studies in mice have shown that genetic disruption of monocyte chemotactic protein-1 or its receptor, 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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