Abstract：
Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. 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 SCN5A 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 SCN5A 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%) SCN5A+(44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-.SCN5A 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 SCN5A- (11.4% versus 3%, P=0.023). The proportion of females was higher among patients with P/LP compared with SCN5A- (18.2% versus 6.3%, P=0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A- (41.9% versus 16.8%, P<0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P<0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P<0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P=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 SCN5A-. 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.
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 SCN5A 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%) SCN5A+(44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-.SCN5A 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 SCN5A- (11.4% versus 3%, P=0.023). The proportion of females was higher among patients with P/LP compared with SCN5A- (18.2% versus 6.3%, P=0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A- (41.9% versus 16.8%, P<0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P<0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P<0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P=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 SCN5A-. 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.
摘要：
Brugada综合征（BrS）与心脏钠通道基因突变有关，SCN5A.然而,有心律失常事件的BrS患者的遗传学研究有限.我们试图比较各种临床，心电图,和根据SCN5A基因型的电生理参数，在患有首次心律失常事件的大量BrS先证者队列中。
关于Brugada综合征心律失常事件的调查是对10个西方国家和4个亚洲国家的调查，收集678例首次发生心律失常的BrS患者。只包括先证者，和SCN5A基因型裁定。没有适当遗传数据的患者被排除在外。分析基因型与临床特征的关联。
研究组包括392个先证者：92个（23.5%）SCN5A+（44个致病/可能致病[P/LP]和48个未知意义的变异）和300个（76.5%）SCN5A-。SCN5A错义变体和托管它们的患者相似，无论判决如何。与SCN5A-相比，P/LP患者的儿科（<16岁）比例更高（11.4％对3％，P=0.023)。与SCN5A-相比，P/LP患者中女性的比例更高（18.2％对6.3％，P=0.013)。与SCN5A-相比，P/LP先证者更可能有心源性猝死家族史(41.9%对16.8%,P<0.001)。与SCN5A-相比，P/LP患者的白人比例更高（87.5％对47％，P<0.001)。种族(赔率比，5.41[2.8-11.19],P<0.001）和心源性猝死家族史（比值比，2.73[1.28-5.82],P=0.009）是逻辑回归后与P/LP基因型相关的独立变量。
BrS的遗传基础与性别有着复杂的关系，种族,和年龄。与SCN5A-患者相比，携带P/LP变体的前带倾向于在更年轻的年龄经历他们的第一次心律失常事件，并且发生由发烧引发的事件。此外,他们更可能是白人，并且有心源性猝死的家族史。在女性中,P/LP变异提示有症状的风险增加.应在大量前瞻性收集的国际队列中，在种族特定的基础上进一步研究这种关联。
关于Brugada综合征心律失常事件的调查是对10个西方国家和4个亚洲国家的调查，收集678例首次发生心律失常的BrS患者。只包括先证者，和SCN5A基因型裁定。没有适当遗传数据的患者被排除在外。分析基因型与临床特征的关联。
研究组包括392个先证者：92个（23.5%）SCN5A+（44个致病/可能致病[P/LP]和48个未知意义的变异）和300个（76.5%）SCN5A-。SCN5A错义变体和托管它们的患者相似，无论判决如何。与SCN5A-相比，P/LP患者的儿科（<16岁）比例更高（11.4％对3％，P=0.023)。与SCN5A-相比，P/LP患者中女性的比例更高（18.2％对6.3％，P=0.013)。与SCN5A-相比，P/LP先证者更可能有心源性猝死家族史(41.9%对16.8%,P<0.001)。与SCN5A-相比，P/LP患者的白人比例更高（87.5％对47％，P<0.001)。种族(赔率比，5.41[2.8-11.19],P<0.001）和心源性猝死家族史（比值比，2.73[1.28-5.82],P=0.009）是逻辑回归后与P/LP基因型相关的独立变量。
BrS的遗传基础与性别有着复杂的关系，种族,和年龄。与SCN5A-患者相比，携带P/LP变体的前带倾向于在更年轻的年龄经历他们的第一次心律失常事件，并且发生由发烧引发的事件。此外,他们更可能是白人，并且有心源性猝死的家族史。在女性中,P/LP变异提示有症状的风险增加.应在大量前瞻性收集的国际队列中，在种族特定的基础上进一步研究这种关联。
