Research Programs Unit, Molecular Medicine and Department of Medicine, University of Helsinki, Helsinki, Finland.
PLoS One. 2012;7(7):e41675. doi: 10.1371/journal.pone.0041675. Epub 2012 Jul 23.
Sudden cardiac death (SCD) accounts for up to half of cardiac mortality. The risk of SCD is heritable but the underlying genetic variants are largely unknown. We investigated whether common genetic variants predisposing to arrhythmia or related electrocardiographic phenotypes, including QT-interval prolongation, are associated with increased risk of SCD.
METHODOLOGY/PRINCIPAL FINDINGS: We studied the association between 28 candidate SNPs and SCD in a meta-analysis of four population cohorts (FINRISK 1992, 1997, 2002 and Health 2000, n = 27,629) and two forensic autopsy series (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 694). We also studied the association between established cardiovascular risk factors and SCD. Causes of death were reviewed using registry-based health and autopsy data. Cox regression and logistic regression models were adjusted for age, sex, and geographic region. The total number of SCDs was 716. Two novel SNPs were associated with SCD: SCN5A rs41312391 (relative risk [RR] 1.27 per minor T allele, 95% CI 1.11-1.45, P = 3.4×10(-4)) and rs2200733 in 4q25 (RR 1.28 per minor T allele, 95% CI 1.11-1.48, P = 7.9×10(-4)). We also replicated the associations for 9p21 (rs2383207, RR 1.13 per G allele, 95% CI 1.01-1.26, P = 0.036), as well as for male sex, systolic blood pressure, diabetes, cigarette smoking, low physical activity, coronary heart disease, and digoxin use (P<0.05).
CONCLUSIONS/SIGNIFICANCE: Two novel genetic variants, one in the cardiac sodium channel gene SCN5A and another at 4q25 previously associated with atrial fibrillation, are associated with SCD.
心脏性猝死（SCD）占心脏性死亡的一半以上。SCD 的风险是可遗传的，但潜在的遗传变异在很大程度上是未知的。我们研究了导致心律失常或相关心电图表型（包括 QT 间期延长）的常见遗传变异是否与 SCD 风险增加相关。
方法/主要发现：我们在四个人群队列（芬兰 1992、1997、2002 和健康 2000 年，n=27629）和两个法医解剖系列（赫尔辛基猝死研究和坦佩雷解剖研究，n=694）的荟萃分析中研究了 28 个候选单核苷酸多态性与 SCD 之间的关联。我们还研究了已确立的心血管危险因素与 SCD 之间的关联。使用基于登记的健康和尸检数据审查死因。Cox 回归和逻辑回归模型调整了年龄、性别和地理位置。SCD 总人数为 716 人。两个新的 SNP 与 SCD 相关：SCN5A rs41312391（每 minor T 等位基因风险比 [RR]1.27，95%CI1.11-1.45，P=3.4×10(-4)）和 4q25 中的 rs2200733（RR 每 minor T 等位基因 1.28，95%CI1.11-1.48，P=7.9×10(-4)）。我们还复制了 9p21（rs2383207，RR 每 G 等位基因 1.13，95%CI1.01-1.26，P=0.036）、男性、收缩压、糖尿病、吸烟、低体力活动、冠心病和地高辛使用的相关性（P<0.05）。
结论/意义：两个新的遗传变异，一个位于心脏钠离子通道基因 SCN5A 中，另一个位于以前与心房颤动相关的 4q25，与 SCD 相关。
