Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

• Published in: Scientific Reports
• Main Authors: Lauri Holmström, Katri Pylkäs, Anna Tervasmäki, Juha Vähätalo, Katja Porvari, Lasse Pakanen, Kari S. Kaikkonen, Juha S. Perkiömäki, Antti M. Kiviniemi, Risto Kerkelä, Olavi Ukkola, Robert J. Myerburg, Heikki V. Huikuri, Juhani Junttila
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Portfolio 2021
• Subjects: Medicine; R; Science; Q; Northern Finland
• Online Access: https://doi.org/10.1038/s41598-021-90693-7; https://doaj.org/article/114df0d571394915b5cd3f2ed4d33d2b

Abstract 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.