Lack of association between connexin40 polymorphisms and coronary artery disease

Anna Pfenniger, Sander W. van der Laan, Bernard Foglia, Sylvie Dunoyer-Geindre, Jacques Antoine Haefliger, Stephan Winnik, François Mach, Gerard Pasterkamp, Richard W. James, Brenda R. Kwak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)148-153
Number of pages6
JournalAtherosclerosis
Volume222
Issue number1
DOIs
StatePublished - May 2012

Keywords

  • Atherosclerosis
  • Connexin40
  • Coronary artery disease
  • Gap junction
  • Gene polymorphism
  • Hypertension
  • Plaque stability

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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