title: Connexin37: a potential modifier gene of inflammatory disease.
abstract: There is an increasing appreciation of the importance of gap junction proteins (connexins) in modulating the severity of inflammatory diseases. Multiple epidemiological gene association studies have detected a link between a single nucleotide polymorphism in the human connexin37 (Cx37) gene and coronary artery disease or myocardial infarction in various populations. This C1019T polymorphism causes a proline-to-serine substitution (P319S) in the regulatory C terminal tail of Cx37, a protein that is expressed in the vascular endothelium as well as in monocytes and macrophages. Indeed, these three cell types are key players in atherogenesis. In the early phases of atherosclerosis, blood monocytes are recruited to the sites of injury in response to chemotactic factors. Monocytes adhere to the dysfunctional endothelium and transmigrate across endothelial cells to penetrate the arterial intima. In the intima, monocytes proliferate, mature, and accumulate lipids to progress into macrophage foam cells. This review focuses on Cx37 and its impact on the cellular and molecular events underlying tissue function, with particular emphasis of the contribution of the C1019T polymorphism in atherosclerosis. We will also discuss evidence for a potential mechanism by which allelic variants of Cx37 are differentially predictive of increased risk for inflammatory diseases.
authors.affiliation: Department of Pediatrics, Geneva University Hospitals, 1211, Geneva 14, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Chanson
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
mesh_terms: D000818:Animals; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006331:Heart Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide
chemical_list: D017630:Connexins