Division of Population Health and Computational Medicine, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida; the Geriatric Research Education and Clinical Center, Veterans Affairs Medical Center, Miami, Florida.
Department of Medicine, St Elizabeths Medical Center, Boston, Massachusetts; Universidad Catolica Santiago de Guayaquil, Guayaquil, Ecuador.
Am J Cardiol. 2019 Jun 15;123(12):1900-1905. doi: 10.1016/j.amjcard.2019.02.058. Epub 2019 Mar 20.
The pathophysiology of sudden cardiac death (SCD) remains incompletely understood. Genetic mutations can create a favorable substrate for SCD. Our aim is to evaluate the evidence of single nucleotide polymorphisms (SNPs) as predictors of SCD. We searched the Medline database (2000 to 2017) and selected all case-control or cohort studies that reported associations between SNPs and SCD. Our search terms included "polymorphisms" and "sudden death." We collected the study design, population ethnic background, gene testing strategy, the association between the SNP and SCD, and the cardiovascular comorbidities of the population. Our search yielded 723 studies, of which we included 24 based upon our inclusion criteria. The studies had a total population of 78,165 participants, with a median age of 62.5 years (IQR 56 to 66) and 35% (IQR 13 to 32) were female. Almost all studies were conducted in white patients of European descent and the most commonly used genetic strategy was candidate gene panels. Fifteen of the studies had a case-control design that included SCD patients without known heart disease as the comparison group and the other 9 studies included patients with heart failure and coronary artery disease. The studies evaluated 53 SNPs and the most common genetic loci were SCN5A, RyR2, CASQ2, NOSA1P, and AGTR. SNPs with the 3 strongest statistically significant ORs >1 were: rs6684209 of CASQ2 (odds ratio [OR] 19), rs3814843 of CALM1 (OR 5.5), and rs35594137 of GJA5 (OR 3.6). In Conclusion, many SNPs are associated with SCD, with the strongest associations seen in SNPs of genes related to intracellular calcium handling. These findings were generated primarily using a candidate gene strategy in white patients with European descent.
心脏性猝死（SCD）的病理生理学仍不完全清楚。基因突变可产生有利于 SCD 的基质。我们的目的是评估单核苷酸多态性（SNP）作为 SCD 预测因子的证据。我们检索了 Medline 数据库（2000 年至 2017 年），并选择了所有报告 SNP 与 SCD 之间关联的病例对照或队列研究。我们的检索词包括“多态性”和“猝死”。我们收集了研究设计、人群的种族背景、基因检测策略、SNP 与 SCD 之间的关联以及人群的心血管合并症。我们的检索结果产生了 723 项研究，其中根据纳入标准纳入了 24 项研究。这些研究的总人群为 78165 名参与者，平均年龄为 62.5 岁（IQR 56 至 66），35%（IQR 13 至 32）为女性。几乎所有研究都是在白种欧洲裔患者中进行的，最常用的遗传策略是候选基因面板。15 项研究采用病例对照设计，将无已知心脏病的 SCD 患者作为对照组，另外 9 项研究纳入心力衰竭和冠心病患者。这些研究评估了 53 个 SNP，最常见的遗传基因座是 SCN5A、RyR2、CASQ2、NOSA1P 和 AGTR。具有 3 个最强统计学意义 OR>1 的 SNP 是：CASQ2 的 rs6684209（优势比[OR] 19）、CALM1 的 rs3814843（OR 5.5）和 GJA5 的 rs35594137（OR 3.6）。总之，许多 SNP 与 SCD 相关，与细胞内钙处理相关基因的 SNP 相关性最强。这些发现主要是在具有欧洲血统的白种患者中使用候选基因策略得出的。
