Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Jiangxi Key Laboratory of Molecular Medicine, Nanchang 330006, China.
Clin Genet. 2020 Jan;97(1):198-208. doi: 10.1111/cge.13552. Epub 2019 May 6.
Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis. Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.
SCN5A 突变的存在是否是 BrS 风险的预测因素仍存在争议，且患者选择偏倚可能削弱了之前的发现。因此，我们进行了这项研究，以阐明存在 SCN5A 突变的 BrS 先证者的临床特征和结局。我们系统地检索了截至 2018 年 10 月发表的合格研究。共纳入了 17 项纳入 1780 例 BrS 患者的研究。总的来说，我们的研究结果发现，与没有 SCN5A 突变的 BrS 患者相比，存在 SCN5A 突变的患者发病时年龄更小，自发性 1 型心电图模式的发生率更高，传导或复极异常更为明显，心房易损性增加。此外，SCN5A 突变的存在与亚洲（优势比 [OR] = 1.82，95%置信区间 [CI] 1.07-3.11；P =.03）和高加索人群（OR = 2.24，95%CI 1.02-4.90；P =.04）中主要心律失常事件风险增加相关。总之，存在 SCN5A 突变的患者表现出更明显的电生理缺陷和更严重的预后。在确定 SCN5A 突变状态是否是独立的风险预测因素之前，临床医生在进行风险分层或治疗指导时应谨慎使用基因检测。
