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

Objective-Studies in mice have shown that genetic disruption of monocyte chemotactic protein- I 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 (Val64IIe) 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-IIe64 variant (Val/IIe and IIe/IIe 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.