Koontz Jason I, Haithcock Daniel, Cumbea Valerie, Waldron Anthony, Stricker Kristie, Hughes Amy, Nilsson Kent, Sun Albert, Piccini Jonathan P, Kraus William E, Pitt Geoffrey S, Shah Svati H, Hranitzky Patrick
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Am Heart J. 2009 Nov;158(5):719-25. doi: 10.1016/j.ahj.2009.08.011.
Disturbances in cardiac rhythm can lead to significant morbidity and mortality. Many arrhythmias are known to have a heritable component, but the degree to which genetic variation contributes to disease risk and morbidity is poorly understood.
The EPGEN is a prospective single-center repository that archives DNA, RNA, and protein samples obtained at the time of an electrophysiologic evaluation or intervention. To identify genes and molecular variants that are associated with risk for arrhythmic phenotypes, EPGEN uses unbiased genomic screening; candidate gene analysis; and both unbiased and targeted transcript, protein, and metabolite profiling. To date, EPGEN has successfully enrolled >1,500 subjects. The median age of the study population is 62.9 years; 35% of the subjects are female and 21% are black. To this point, the study population has been composed of patients who had undergone defibrillator (implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator) implantation (45%), electrophysiology studies or ablation procedures (35%), and pacemaker implantation or other procedures (20%). The cohort has a high prevalence of comorbidities, including diabetes (33%), hypertension (73%), chronic kidney disease (26%), and peripheral vascular disease (13%).
We have established a biorepository and clinical database composed of patients with electrophysiologic diseases. EPGEN will seek to (1) improve risk stratification, (2) elucidate mechanisms of arrhythmogenesis, and (3) identify novel pharmacologic targets for the treatment of heart rhythm disorders.
心律失常可导致严重的发病率和死亡率。已知许多心律失常具有遗传成分，但遗传变异对疾病风险和发病率的影响程度尚不清楚。
EPGEN是一个前瞻性单中心储存库，存档在电生理评估或干预时获取的DNA、RNA和蛋白质样本。为了识别与心律失常表型风险相关的基因和分子变异，EPGEN采用无偏倚基因组筛选、候选基因分析以及无偏倚和靶向的转录本、蛋白质和代谢物分析。迄今为止，EPGEN已成功招募了超过1500名受试者。研究人群的中位年龄为62.9岁；35%的受试者为女性，21%为黑人。至此，研究人群包括接受除颤器（植入式心律转复除颤器或心脏再同步治疗除颤器）植入的患者（45%）、电生理研究或消融手术的患者（35%）以及起搏器植入或其他手术的患者（20%）。该队列合并症的患病率很高，包括糖尿病（33%）、高血压（73%）、慢性肾病（26%）和外周血管疾病（13%）。
我们建立了一个由电生理疾病患者组成的生物样本库和临床数据库。EPGEN将致力于（1）改善风险分层，（2）阐明心律失常的发生机制，以及（3）识别治疗心律紊乱的新型药物靶点。
