Leviev Heart Institute, The Chaim Sheba Medical Center, Tel Hashomer, Israel (A. Milman).
Sackler School of Medicine, Tel Aviv University, Israel (A. Milman, A.H., B.B.).
Circ Genom Precis Med. 2021 Oct;14(5):e003222. doi: 10.1161/CIRCGEN.120.003222. Epub 2021 Aug 31.
Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to genotype in a large cohort of BrS probands with first arrhythmic event.
Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed.
The study group comprised 392 probands: 92 (23.5%) (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with (11.4% versus 3%, =0.023). The proportion of females was higher among patients with P/LP compared with - (18.2% versus 6.3%, =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with - (41.9% versus 16.8%, <0.001). A higher proportion of patients with P/LP were White compared with (87.5% versus 47%, <0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], =0.009) were independent variables associated with P/LP genotype following logistic regression.
The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.
Brugada 综合征（BrS）与心脏钠离子通道基因突变有关。然而，具有心律失常事件的 BrS 患者的遗传研究受到限制。我们旨在比较首次心律失常事件的大量 BrS 先证者中根据基因型的各种临床、ECG 和电生理参数。
心律失常事件的 Brugada 综合征调查是一项在 10 个西方国家和 4 个亚洲国家进行的调查，共纳入 678 例首次心律失常事件的 BrS 患者。仅纳入先证者，并进行基因型裁决。排除无适当遗传数据的患者。分析基因型与临床特征的关系。
研究组包括 392 名先证者：92 名（23.5%）（44 个致病性/可能致病性 [P/LP] 和 48 个未知意义的变异）和 300 名（76.5%）错义变异，无论裁决如何，携带这些变异的患者相似。与（11.4%对 3%，=0.023）相比，携带 P/LP 的患者中儿童（<16 岁）的比例更高。与携带（18.2%对 6.3%，=0.013）相比，携带 P/LP 的患者中女性比例更高。与携带（41.9%对 16.8%，<0.001）相比，携带 P/LP 的先证者更有可能有家族性心源性猝死史。与携带（87.5%对 47%，<0.001）相比，携带 P/LP 的患者中白人的比例更高。种族（比值比，5.41[2.8-11.19]，<0.001）和家族性心源性猝死史（比值比，2.73[1.28-5.82]，=0.009）是 logistic 回归后与 P/LP 基因型相关的独立变量。
BrS 的遗传基础与性别、种族和年龄有复杂的关系。携带 P/LP 变异的先证者倾向于在较年轻的年龄发生首次心律失常事件，且与携带的患者相比，更易由发热触发。此外，他们更有可能是白人，并有家族性心源性猝死史。在女性中，P/LP 变异提示有更高的症状发生风险。应在大型前瞻性国际队列中进行基于种族特异性的进一步研究。
