Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification.

Abstract

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.

• Authors: Ana M Valdes, Megan L Wolfe, Eamonn J O'Brien, Nigel K Spurr, Warren Gefter, Andrew Rut, Pieter H E Groot, Daniel J Rader
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 11 Pg. 1924-8 (Nov 01 2002) ISSN: 1524-4636 [Electronic] United States
• PMID: 12426226 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CCR2 protein, human
• Receptors, CCR2
• Receptors, Chemokine
• Isoleucine
• Valine

Topics

• Adult
• Aged
• Amino Acid Substitution (genetics)
• Calcinosis (genetics)
• Cardiomyopathies (genetics)
• Coronary Vessels (chemistry, metabolism, pathology)
• Female
• Genotype
• Humans
• Isoleucine (genetics)
• Male
• Middle Aged
• Models, Statistical
• Polymorphism, Genetic (genetics)
• Receptors, CCR2
• Receptors, Chemokine (genetics)
• Sex Factors
• Valine (genetics)