Association between C1019T polymorphism of connexin37 and acute myocardial infarction: a study in patients from Sicily.

During atherogenesis, a critical role is played by intercellular communication via gap junctions, cell membrane channels linking the cytoplasmic compartments of adjacent cells. The component protein subunits of these channels, called connexin (Cx), belong to a multigene family. Cx37 is involved in growth, regeneration after injury and ageing of the endothelial cells, suggesting its role in atherosclerosis. The C1019 single nucleotide polymorphism (SNP) of Cx37 gene was associated with thickening of the carotid intima in Swedish men and was also associated with coronary artery disease in a Taiwanese population. On the other hand, in two more recent studies performed in male Japanese population, T1019 Cx37 SNP has shown to be a risk factor for acute myocardial infarction (AMI). In the light of these discrepant results, we have studied the frequency of this SNP in a very homogeneous cohort of young male people affected by AMI. We analysed 97 male Sicilian patients (mean age 40, age range 20-46) and 196 healthy male controls (mean age 39, age range 20-55) for C1019T of the Cx37. The 1019T SNP was significantly increased in the patients compared to the controls (43.8% vs. 34.4%; p=0.03 by chi2 test with Yates' correction; odds ratio (OR) 1.5, (1.0-2.1) 95% confidence interval (CI)). The present case control study performed in a homogeneous Caucasoid population confirms the Japanese results that T SNP of Cx37 gene is involved in AMI phenotype, demonstrating the consistency of the association across past studies and across different populations. The differences between patients and controls are significant but relatively small with an odd ratio risk of 1.5. However, as AMI is a multifactorial disease, any single mutation will only provide a small or modest contribution to risk, also depending on interaction with other genes and/or a particular environment.