Association between androgen receptor gene CAG repeat and KATP channel Kir6.2 gene E23K polymorphisms and susceptibility to coronary artery disease and in vitro vasodilatation responses of testosterone

Coronary artery disease (CAD) is the leading cause of death among both men andwomen. Testosterone provides rapid improvements in myocardial ischemia, an effectpresumably mediated by testosterone-induced coronary vasodilatation. Thetestosterone-induced vasodilatation is mediated by potassium channels (KATP: ATPsensitive K+channels and Ca-activated K+ channels) and membrane-dependentandrogen receptors.A polymorphic CAG trinucleotide repeat sequence in AR gene and an E23Kpolymorphism in Kir6.2 gene of ATP-sensitive potassium channels have been detectedrecently.In our study, we aimed to investigate the impact of both polymorphisms ontestosterone-induced vasodilatation in internal mammary artery rings from patients withCAD undergoing coronary bypass surgery. Determination of the number of CAGrepeats were performed by Gene-Scan analyses. The upper quartile of CAG length was?17. We did not find any association between androgen receptor CAG repeats orgenotypes of E23K polymorphisms of Kir6.2 gene and testosterone-induced (10-7, 10-6,10-5.5, 10-5, 10-4.5, 10-4, 10-3.5M) vasodilatation responses or their ED50 in IMA.In an other part of our study a group of 340 patients with CAD and 91 controlsubjects were analysed for the E23K (G----A) polymorphism in Kir6.2 gene bypolymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP)assays.Among the CAD patients, the freguency of the G allele (wild type) wassignificantly higher compared to control subjects (CAD 58.2% vs control 47.8%,p<0.05). Additionally, there were statistically significant differences in GG andGA+AA genotypes frequencies between CAD and control group (35.9% vs 23.1%, and64.1% vs 76.9%, p=0.02).In conclusion, E23K polymorphism of Kir6.2 gene and CAG repeat polymorphismin AR gene may not have a role in testosterone-induced vasodilatations. However, theE23K gene polymorphism in Kir6.2 gene may confer susceptibility to CAD.Key Words: Coronary artery disease, Internal mammary artery, Androgen receptorgene CAG repeat, KATP channel Kir6.2 gene E23K polymorphism.