Paolo Severino 1 , Andrea D'Amato 1 , Lucrezia Netti 1 , Mariateresa Pucci 1 , Marco V Mariani 1 , Sara Cimino 1 , Lucia I Birtolo 1 , Fabio Infusino 1 , Paolo De Orchi 1 , Raffaele Palmirotta 2 , Domenica Lovero 2 , Franco Silvestris 2 , Viviana Caputo 3 , Antonio Pizzuti 3 , Fabio Miraldi 1 , Viviana Maestrini 1 , Massimo Mancone 1 , Francesco Fedele 1 Show Affiliations »
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. © The European Society of Cardiology 2020.
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 . © The European Society of Cardiology 2020.
Entities: Disease
Gene
Mutation
Species
Keywords:
ATP-sensitive potassium channel; Ion channels; coronary artery disease; coronary microvascular dysfunction; ischaemic heart disease; single nucleotide polymorphisms
Year: 2020
PMID： 33611546 DOI： 10.1177/2047487320926780
Source DB: PubMed Journal: Eur J Prev Cardiol ISSN： 2047-4873 Impact factor: 7.804