Susceptibility to ischaemic heart disease: Focusing on genetic variants for ATP-sensitive potassium channel beyond traditional risk factors

Paolo Severino; Andrea D'Amato; Lucrezia Netti; Mariateresa Pucci; Marco V Mariani; Sara Cimino; Lucia I Birtolo; Fabio Infusino; Paolo De Orchi; Raffaele Palmirotta; Domenica Lovero; Franco Silvestris; Viviana Caputo; Antonio Pizzuti; Fabio Miraldi; Viviana Maestrini; Massimo Mancone; Francesco Fedele

doi:10.1177/2047487320926780

Susceptibility to ischaemic heart disease: Focusing on genetic variants for ATP-sensitive potassium channel beyond traditional risk factors

Eur J Prev Cardiol. 2021 Oct 25;28(13):1495-1500. doi: 10.1177/2047487320926780.

Authors

Paolo Severino¹, Andrea D'Amato¹, Lucrezia Netti¹, Mariateresa Pucci¹, Marco V Mariani¹, Sara Cimino¹, Lucia I Birtolo¹, Fabio Infusino¹, Paolo De Orchi¹, Raffaele Palmirotta², Domenica Lovero², Franco Silvestris², Viviana Caputo³, Antonio Pizzuti³, Fabio Miraldi¹, Viviana Maestrini¹, Massimo Mancone¹, Francesco Fedele¹

Affiliations

¹ Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Italy.
² Section of Clinical and Molecular Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Italy.
³ Department of Experimental Medicine, Sapienza University of Rome, Policlinico Umberto I Hospital, Italy.

PMID: 33611546
DOI: 10.1177/2047487320926780

Abstract

Aims: Ischaemic heart disease is classically associated with coronary artery disease. Recent evidences showed the correlation between coronary microvascular dysfunction and ischaemic heart disease, even independently of coronary artery disease. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), are reported to be involved in ischaemic heart disease susceptibility. The aim of the present study is to evaluate the role of KATP channel and its genetic variants in patients with ischaemic heart disease and evaluate whether differences exist between coronary artery disease and coronary microvascular dysfunction.

Methods: A total of 603 consecutive patients with indication for coronary angiography due to suspected myocardial ischaemia were enrolled. Patients were divided into three groups: coronary artery disease (G1), coronary microvascular dysfunction (G2) and normal coronary arteries (G3). Analysis of four single nucleotide polymorphisms (rs5215, rs5216, rs5218 and rs5219) of the KCNJ11 gene encoding for Kir6.2 subunit of the KATP channel was performed.

Results: rs5215 A/A and G/A were significantly more represented in G1, while rs5215 G/G was significantly more represented in G3, rs5216 G/G and C/C were both more represented in G3, rs5218 C/C was more represented in G1 and rs5219 G/A was more represented in G1, while rs5219 G/G was significantly more represented in G2. At multivariate analysis, single nucleotide polymorphism rs5215_G/G seems to represent an ischaemic heart disease independent protective factor.

Conclusions: These results suggest the potential role of KATP genetic variants in ischaemic heart disease susceptibility, as an independent protective factor. They may lead to a future perspective for gene therapy against ischaemic heart disease.

Keywords: ATP-sensitive potassium channel; Ion channels; coronary artery disease; coronary microvascular dysfunction; ischaemic heart disease; single nucleotide polymorphisms.