Arteriosclerosis, thrombosis, and vascular biology · 2002
Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification.
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Valdes Ana M, Wolfe Megan L, O'Brien Eamonn J, Spurr Nigel K, Gefter Warren, Rut Andrew, Groot Pieter H E, Rader Daniel J
Аннотация
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.
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.