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-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.


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.
Valdes
Ana M
AM
GlaxoSmithKline, Stevenage, Hertfordshire, UK.
Wolfe
Megan L
ML
O'Brien
Eamonn J
EJ
Spurr
Nigel K
NK
Gefter
Warren
W
Rut
Andrew
A
Groot
Pieter H E
PH
Rader
Daniel J
DJ
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D002114:Calcinosis / Q000235:genetics*; D009202:Cardiomyopathies / Q000235:genetics*; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011110:Polymorphism, Genetic / Q000235:genetics*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D012737:Sex Factors; D014633:Valine / Q000235:genetics*
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D007532:Isoleucine; D014633:Valine