Abstract 18449: Genetic Variants for Katp Channels as Protective Factors in Ischemic Heart Disease Susceptibility: Gender Differences

Abstract

Background: Coronary artery disease has been widely considered a “man’s disease” and not a major concern for women. However, scientists have been trying to unlock the female physiology of ischemic heart disease (IHD). In fact, women are more prone than men to microvascular coronary dysfunction. Recently, we proposed that genetic polymorphisms (SNP) of coronary ion channels may be involved in IHD susceptibility. Our published data showed that the genotype distribution of SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels moderately deviated from the HW equilibrium and that rs5215_GG is correlated with IHD susceptibility. In particular, we described that rs5215_GG genotype of Kir6.2 might have a ‘‘protective’’ role in IHD genesis. Aim and methods: In order to better describe the role of SNP rs5215_GG in IHD susceptibility in woman, we conducted a gender difference in term of prevalence of rs5215_GG on our previous population, i.e. 242 patients with acute coronary syndrome or stable angina, of which 155 with CAD, 46 with microvascular dysfunction and 41 with anatomically and functionally normal coronary arteries. Results: Among 242 patients, rs5215_GG was found to be more frequent in women (16/82; 19.51%; p=0.0450) compared to men. In particular, rs5215_GG was more frequent in female patients with anatomically and functionally normal coronary arteries (8/24; 33.3%; p=0.0428) compared with women with CAD, whereas there was no difference between men in normal and CAD groups. Discussion and conclusion: The polymorphism rs5215_GG is a missense SNP (ATC-GTC) that results in the substitution of isoleucine (I) residue with valine (V) in the Kir6.2 subunit of KATP channels. Our data validate the hypothesis that rs5215_GG could reduce susceptibility to IHD. In fact, rs5215_GG was confirmed to be present more frequently in woman presenting anatomically and functionally normal coronary arteries. Our results suggest that coronary KATP channels expressing rs5215_GG play a protective key role against IHD. Our data endorse the prospect of associations between SNP encoding coronary ion channels and IHD, validating the idea that ion channels play in coronary homeostasis and that their polymorphisms act in IHD genesis.