Francia Pietro, Adduci Carmen, Semprini Lorenzo, Stanzione Rosita, Serdoz Andrea, Caprinozzi Massimo, Santini Daria, Cotugno Maria, Palano Francesca, Musumeci Maria Beatrice, Rubattu Speranza, Volpe Massimo
Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University, Rome.
I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
J Cardiovasc Electrophysiol. 2015 Jun;26(6):656-61. doi: 10.1111/jce.12658. Epub 2015 May 1.
Cardiac ryanodine receptor 2 (RyR2) is critical to the electrical homeostasis of cardiomyocytes. Its gene variant rs3766871 entails channel destabilization and enhanced intracellular Ca(2+) oscillation, thus promoting cardiac arrhythmias. We investigated whether the RyR2 rs3766871 variant is associated with aborted sudden cardiac death or ICD therapy for ventricular tachycardia (VT)/fibrillation (VF) in heart failure (HF) patients implanted with a cardioverter defibrillator (ICD).
A total of 183 HF patients with primary or secondary prevention ICD were divided in 2 groups. A VT/VF group was composed of secondary prevention patients and primary prevention patients with appropriate ICD intervention for VT/VF. An ICD control group was composed of primary prevention patients free from any appropriate ICD intervention after 43 ± 25 months follow-up. Study subjects were genotyped with respect to the rs3766871 RyR2 gene variant. Hazard ratios (HRs) were derived from Cox proportional-hazards regression analysis. In all, 56 patients constituted the VT/VF group and 127 patients the ICD control group. Male sex (HR: 3.02; 95% CI: 0.99-9.18; P = 0.05), atrial fibrillation (AF; HR: 2.33; 95% CI: 0.89-6.10; P = 0.08), and underuse of β-blockers (HR: 2.08; 95% CI: 0.84-5.15; P = 0.11) were associated with the VT/VF phenotype. Prevalence of the rs3766871 minor allele was 2.8% in ICD control patients and 8.0% in the VT/VF group (P = 0.02). After adjustment for age, sex, AF, and use of β-blockers, the rs3766871 minor allele was associated with increased risk of VT/VF (HR: 3.49; 95% CI: 1.14-10.62; P = 0.02).
Our study identifies a significant role of RyR2 rs3766871 minor allele for increased susceptibility to VT/VF in a population of ICD patients with HF.
心肌兰尼碱受体2（RyR2）对心肌细胞的电稳态至关重要。其基因变异rs3766871会导致通道不稳定并增强细胞内Ca(2+)振荡，从而促进心律失常。我们研究了RyR2 rs3766871变异是否与植入心脏复律除颤器（ICD）的心力衰竭（HF）患者的心源性猝死未遂或室性心动过速（VT）/心室颤动（VF）的ICD治疗相关。
总共183例接受一级或二级预防ICD的HF患者被分为两组。VT/VF组由二级预防患者和因VT/VF接受适当ICD干预的一级预防患者组成。ICD对照组由在43±25个月随访后未接受任何适当ICD干预的一级预防患者组成。对研究对象进行RyR2基因变异rs3766871的基因分型。风险比（HR）来自Cox比例风险回归分析。总共56例患者构成VT/VF组，127例患者构成ICD对照组。男性（HR：3.02；95%CI：0.99-9.18；P = 0.05）、心房颤动（AF；HR：2.33；95%CI：0.89-6.10；P = 0.08）和β受体阻滞剂使用不足（HR：2.08；95%CI：0.84-5.15；P = 0.11）与VT/VF表型相关。rs3766871次要等位基因在ICD对照患者中的患病率为2.8%，在VT/VF组中为8.0%（P = 0.02）。在对年龄、性别、AF和β受体阻滞剂使用情况进行调整后，rs3766871次要等位基因与VT/VF风险增加相关（HR：3.49；95%CI：1.14-10.62；P = 0.02）。
我们的研究确定了RyR2 rs3766871次要等位基因在ICD治疗的HF患者群体中对VT/VF易感性增加方面的重要作用。
