Genetic variants associated with cardiac hypertrophy-related sudden cardiac death and cardiovascular outcomes in a Finnish population.

Autor:	Doedens A; Faculty of Medicine, University of Oulu, Oulu, Finland., Skarp S; Faculty of Medicine, University of Oulu, Oulu, Finland sini.skarp@oulu.fi., Holmström L; University of Oulu, Oulu, Finland., Pakanen L; Department of Forensic Medicine, Oulu University Hospital, Oulu, Finland., Saarimäki S; Faculty of Medicine, University of Oulu, Oulu, Finland., Kerkelä R; Research Unit of Biomedicine, University of Oulu, Oulu, Finland., Pylkäs K; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, Oulu, Finland., Huikuri HV; Department of Internal Medicine, University of Oulu, Oulu, Finland., Junttila J; MRC Oulu, Oulun Yliopisto, Oulu, Finland.
Jazyk:	angličtina
Zdroj:	Heart (British Cardiac Society) [Heart] 2024 Oct 03. Date of Electronic Publication: 2024 Oct 03.
DOI:	10.1136/heartjnl-2024-324623
Abstrakt:	Background: Hypertrophic cardiomyopathy is a common cause of non-ischaemic sudden cardiac death (SCD). Left ventricular hypertrophy (LVH) without cardiomyopathy-related myocardial disarray is a common autopsy finding and is often associated with prior hypertension in SCD subjects. Our aim was to investigate novel rare gene variants among SCD subjects with presumably hypertension-related LVH and myocardial fibrosis at autopsy. Methods: Whole exome sequencing was used to study rare variants (minor allele frequency<0.005) estimated to be deleterious in 96 non-ischaemic SCD subjects with presumably hypertension-related LVH and myocardial fibrosis. Associations of the identified variants with cardiac disease endpoints were replicated in the Finnish national genetic study (FinnGen) dataset. Results: 18 variants were estimated likely to affect protein function and 14 of these were associated with cardiomyopathies, heart failure, conduction abnormalities, hypertension and/or cardiac arrest in Finnish population (FinnGen). Three of the variants were classified as pathogenic or likely pathogenic. These include the splice site variant NM_000449.3:c.234-1G>A in regulatory factor X5 and frameshift variants NM_000449.3:c.234-1G>A in dehydrogenase/reductase 7C and NM_015873.3:c.1164del in villin like. Conclusions: We identified rare deleterious variants associated with LVH in SCD subjects. Several of the identified rare variants associated with cardiovascular endpoints including heart failure, cardiomyopathies, cardiac arrest and hypertension in general population. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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