Mutations of the Connexin 37 and 40 Gap-Junction Genes in Patients with Acute Myocardial Infarction

Cx37C1019T Polymorphism May Contribute to the Pathogenesis of Coronary Heart Disease

“…Consequently, these channels providing cell communication could infer the potential role of Cx37 in the development of atherosclerosis (Morel et al, 2009). It has been demonstrated that Cx37 C1019T polymorphism, replacing a cytosine by thymine, may cause a rather nonconservative amino acid change in the regulatory carboxy-terminus of human Cx37 protein, namely, a proline to serine substitution (Incalcaterra et al, 2010;Seifi et al, 2013). Moreover, the lack of Cx37 expression usually resulted in the occurrence of vascular functional defects or morphological changes ( Johnstone et al, 2009).…”

“…1). Finally, 9 clinical case-control studies with a total of 1426 CHD patients and 929 healthy controls met our inclusion criteria for qualitative data analysis (Yeh et al, 2001;Yamada et al, 2002;Listi et al, 2005;Xie et al, 2006;Wong et al, 2007;Han et al, 2008;Zhang et al, 2009;Feng et al, 2010;Seifi et al, 2013). Publication years of the eligible studies ranged from 2001 to 2013.…”

“…Cx37, (gap junction protein, alpha 4, also commonly known as GJA4), is a gap junction protein belonging to the Connexin family, which is normally expressed in various immune cell types, such as endothelial cells, monocytes, and macrophage foam cells, suggesting an important role of these proteins in gap junction-mediated antigen transport and intercellular communication in the immune system (Koutsoumpas et al, 2011;Juo et al, 2012). Generally, Cx37 could form gap junction channels and hemichannels, and then distinctively influence permeability for a variety of signaling molecules, and provide a means for direct cell-cell and cell-extracellular communication, which has been implicated in many important biological events intimately linked to atherogenesis (Wong et al, 2007;Seifi et al, 2013).…”

“…Recently, epidemiologic studies have suggested that connexin 37 (Cx37), which may play a crucial role in atherosclerosis, may be closely associated with the risk of CHD (Han et al, 2008;Seifi et al, 2013). Cx37, (gap junction protein, alpha 4, also commonly known as GJA4), is a gap junction protein belonging to the Connexin family, which is normally expressed in various immune cell types, such as endothelial cells, monocytes, and macrophage foam cells, suggesting an important role of these proteins in gap junction-mediated antigen transport and intercellular communication in the immune system (Koutsoumpas et al, 2011;Juo et al, 2012).…”

Mutations in cardiovascular connexin genes

“…However, these findings could not be confirmed in a larger Swiss population (Pfenniger et al., ). Moreover, despite a clear anti‐atherogenic role of Cx40 in mice (Chadjichristos et al., ), recent studies could also not detect an association of Cx40 promoter polymorphisms and coronary artery disease (CAD), atherosclerotic plaque stability or acute MI in Swiss, Dutch or Iranian populations (Pfenniger et al., ; Seifi et al., ). Altogether, it seems that Cx polymorphisms affecting channel function, such as the Cx37 C1019T polymorphism (see below), may be of greater importance for vascular diseases than polymorphisms affecting the expression level of the protein like the Cx40 promoter polymorphisms.…”