在心脏节律综合征的异质子集中,已经鉴定出心脏钠通道α亚基的该基因中的几种突变。包括Brugada综合征,进行性心脏传导缺陷,病态窦房结综合征,心房颤动和扩张型心肌病。我们研究的目的是将某些SCN5A多态性变异体与经植入式心脏复律除颤器治疗的非LQTS室颤/扑动患者的确诊冠状动脉狭窄直接相关。
方法:一组32个无关个体,年龄63±12岁,包括在研究中。所有患者都接受了检查,诊断和治疗的植入式心律转复除颤器在内科内科,教师医院布尔诺。对照组包括87名年龄相仿的人,没有冠状动脉循环受累,这在日冕上得到了证实。根据标准方案从外周血样品中提取基因组DNA。检查了两个与患者冠状动脉狭窄相关的SCN5A多态性-IVS9-3C/A(rs41312433)和A1673G(rs1805124,H558R)。
结果:在病例对照研究中,在严重心律失常患者和健康人之间,IVS9-3c>a和A1673G基因多态性的基因型分布/等位基因频率没有显着差异。根据心律失常患者的射血分数,SCN5A双基因型的分布在不同类型的心律失常中没有显着差异(p=0.396)。发现射血分数低于40%的室性心律失常在具有临床有效敏感性的多发性冠状动脉狭窄患者中的发生率为10.67倍。特异性和功率测试。在基因型-表型研究中,在重度心律失常患者中,我们观察到两种SCN5A多态性与冠状动脉狭窄之间存在显著关联.多态性IVS9-3C/A的双基因型与A1673G(CCAA)及其简单基因型与冠状动脉多发狭窄(MVS)相关,具有较高的敏感性和特异性(p=0.05;OR=5(95%CI0.99-23.34);敏感性0.70;特异性0.682;功率检验0.359)此外,当具体的狭窄冠状动脉与SCN5A基因型相关时,在右冠状动脉(RCA)有显著狭窄的患者中,CCAA双基因型的发生频率是无冠状动脉病变患者的5倍(p=0.05;OR=5(95%CI0.99~23.34);敏感性0.682;特异性0.700;功效检验0.359).在没有RCA折磨的MVS患者中,CCAA基因型也更常见(p=0.008);患有ACD但没有MVS的患者(p=0.008);与没有ACD折磨和MVS的患者相比,患有ACD折磨和MVS的患者(p=0.005)。
结论:我们的研究表明SCN5A的两个多态性与潜在致命性室性心律失常患者的显著冠状动脉狭窄之间存在高度敏感和特异的关联。同时,这些多态性与心律失常本身无关.因此,SCN5A基因多态变异可能构成生殖细胞基因对缺血的易感部分。
Several mutations in this gene for the α subunit of the cardiac sodium channel have been identified in a heterogeneous subset of cardiac rhythm syndromes, including Brugada syndrome, progressive cardiac conduction defect, sick sinus node syndrome, atrial fibrillation and dilated cardiomyopathy. The aim of our study was to associate some
SCN5A polymorphic variants directly with confirmed coronary stenoses in patients with non-LQTS ventricular fibrillation/flutter treated by an implantable cardioverter defibrillator.
A group of 32 unrelated individuals, aged 63 ± 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two
SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients.
In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both
SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005).
Our study presents a highly sensitive and specific association of two polymorphisms in
SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus,
SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.