Abstract 19305: Diabetes Mellitus and Ischemic Heart Disease Susceptibility: Which is the Influence of Genetic Polymorphisms for Katp Channels?

Abstract

Background: Evidences show that diabetes mellitus (DM) lead to higher risk for ischemic heart disease (IHD). Recently, we proposed that genetic polymorphisms (SNP) of coronary ion channels might be involved in IHD. We 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 linked to IHD susceptibility: it might have a ‘‘protective’’ role in IHD genesis. Moreover, previous studies described that SNP rs5215_GG is strongly correlated with DM and hyperinsulinism in human. Aim and methods: In the present study, we hypothesized that SNP rs5215_GG for Kir6.2 subunit for KATP channels had some influences in the susceptibility of DM to IHD. We performed a subgroup analysis about the influence of rs5215_GG in diabetic patients on our previous population, i.e. 242 patients candidates to elective or emergency coronary angiography for acute coronary syndrome or chronic angina, of which 155 with CAD, 46 with microvascular dysfunction and 41 with anatomically and functionally normal coronary arteries (control group). Results: Among 242 patients, comparing subjects with DM to those without, there was not any significant difference in the prevalence of rs5215_GG. However, among 33 subjects without DM with normal coronary arteries, SNP rs5215_GG had a higher prevalence compared to those in the CAD group (10/33; 30.3%; p= 0.0277) as well as non-diabetic patients in the microvascular dysfunction group (9/33; 27.2%; p= 0.0295). Discussion and conclusion: The variant rs5215_GG results in the substitution of isoleucine (I) residue with valine (V) in the Kir6.2 subunit of KATP channels. Our results confirm that rs5215_GG might decrease susceptibility to IHD in patients without DM. In fact, rs5215_GG was confirmed to be present more frequently in patients without DM presenting anatomically and functionally normal coronary arteries. We believe that absence of DM is protective against IHD genesis and it might be improved by coronary KATP channels expressing rs5215_GG. Taken together, our data ratify the possibility that ion channels play a key role in coronary homeostasis and that SNP encoding for ion channels are involved in IHD pathophysiology.