title: 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.
  
  
  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.affiliation: GlaxoSmithKline, Stevenage, Hertfordshire, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Megan L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Eamonn J
authors.initials: EJ
authors.lastname: O'Brien
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Spurr
authors.forename: Warren
authors.initials: W
authors.lastname: Gefter
authors.forename: Andrew
authors.initials: A
authors.lastname: Rut
authors.forename: Pieter H E
authors.initials: PH
authors.lastname: Groot
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: 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*
chemical_list: C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D007532:Isoleucine; D014633:Valine