title: Lack of association between connexin40 polymorphisms and coronary artery disease.
abstract: OBJECTIVE
  Cx40 is a gap junction protein important for cell-cell communication in the endothelium. Polymorphisms in the promoter region of the human Cx40 gene, -44G>A and +71A>G, were shown to reduce Cx40 transcription by half. As mice with an endothelial-specific deletion of Cx40 are more susceptible to atherosclerosis, this study was designed to discover a correlation between these polymorphisms and atherosclerosis in European populations.
  
  
  RESULTS
  803 patients referred to the Geneva University Hospitals for elective coronary angiography were divided according to the number of significantly stenosed vessels (from 0 to 3) and were genotyped for the Cx40 polymorphisms. Genotype distribution in the control group was -44GG/+71AA=59.8%, -44AG/+71AG=35.1% and -44AA/+71GG=5.2%. Surprisingly, this distribution was similar in the CAD group, with -44GG/+71AA=58.5%, -44AG/+71AG=37.6% and -44AA/+71GG=3.8% (p=0.67). Moreover, no significant association between histological carotid plaque composition of culprit lesions and Cx40 polymorphisms could be detected in 583 Dutch patients of the Athero-Express study.
  
  
  CONCLUSIONS
  Despite a clear antiatherogenic role of Cx40 in mice, our study could not detect an association of Cx40 promoter polymorphisms and CAD in human. Moreover, a correlation with atherosclerotic plaque stability or hypertension could not be demonstrated either. Connexin polymorphisms affecting channel function may be of greater importance for cardiovascular disease than polymorphisms affecting the expression level of the protein.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland. anna.pfenniger@unige.ch
authors.forename: Anna
authors.initials: A
authors.lastname: Pfenniger
authors.forename: Sander W
authors.initials: SW
authors.lastname: van der Laan
authors.forename: Bernard
authors.initials: B
authors.lastname: Foglia
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dunoyer-Geindre
authors.forename: Jacques-Antoine
authors.initials: JA
authors.lastname: Haefliger
authors.forename: Stephan
authors.initials: S
authors.lastname: Winnik
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
mesh_terms: D000368:Aged; D017630:Connexins / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein