Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, PO Box 5000, 90014, Oulu, Finland.
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, Oulu, Finland.
Sci Rep. 2021 May 27;11(1):11171. doi: 10.1038/s41598-021-90693-7.
The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.
遗传变异在由获得性心肌疾病引起的非缺血性心源性猝死（SCD）中的作用尚不清楚。我们研究了患有高血压/肥胖相关肥厚性心肌疾病的 SCD 患者是否存在潜在的与疾病相关的基因变异。Fingesture 研究从芬兰北部收集了 5869 例尸检证实的 SCD 患者的数据。在 SCD 患者中，有 740 例（13%）患有高血压和/或肥胖症，这是肥厚性和纤维化心肌疾病的最可能解释。我们对 151 名具有最佳 DNA 质量的此类患者使用 174 个心脏基因的面板进行了下一代测序。我们使用了 48 名患有高血压和肥厚性心脏病的患者作为对照。在 15 名 SCD 患者（10%）中发现了可能致病的变异，在另外 43 名 SCD 患者（28%）中观察到了意义不明的变异（VUS）。在对照组中，有 2 名受试者（4%；p=0.21）存在可能致病的变异，有 12 名受试者（25%；p=0.64）存在 VUS。在 SCD 患者中，存在潜在疾病相关变异与平均 BMI 和心脏重量较低有关。潜在的疾病相关基因变异在非缺血性 SCD 中很常见，但需要进一步研究来确定罕见遗传变异对导致 SCD 的获得性心肌疾病程度的具体贡献。
