缺血性心脏病易感性：聚焦于传统危险因素之外的ATP敏感性钾通道基因变异

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

作者信息

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

机构信息

Department of Clinical, Internal, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Italy.

Section of Clinical and Molecular Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Italy.

出版信息

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

DOI:10.1177/2047487320926780

PMID:33611546

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.

摘要

目的

缺血性心脏病通常与冠状动脉疾病相关。最近的证据表明冠状动脉微血管功能障碍与缺血性心脏病之间存在关联，甚至独立于冠状动脉疾病。离子通道是血流调节机制的最终效应器，据报道其基因变异，特别是ATP敏感性钾通道（KATP）的Kir6.2亚基的基因变异，与缺血性心脏病易感性有关。本研究的目的是评估KATP通道及其基因变异在缺血性心脏病患者中的作用，并评估冠状动脉疾病和冠状动脉微血管功能障碍之间是否存在差异。

方法

共纳入603例因疑似心肌缺血而有冠状动脉造影指征的连续患者。患者分为三组：冠状动脉疾病组（G1）、冠状动脉微血管功能障碍组（G2）和冠状动脉正常组（G3）。对编码KATP通道Kir6.2亚基的KCNJ11基因的四个单核苷酸多态性（rs5215、rs5216、rs5218和rs5219）进行分析。

结果

rs5215 A/A和G/A在G1组中显著更常见，而rs5215 G/G在G3组中显著更常见，rs5216 G/G和C/C在G3组中均更常见，rs5218 C/C在G1组中更常见，rs5219 G/A在G1组中更常见，而rs5219 G/G在G2组中显著更常见。在多变量分析中，单核苷酸多态性rs5215_G/G似乎是缺血性心脏病的独立保护因素。