Mitochondrial DNA variation in sudden cardiac death: a population-based study

Laura Kytövuori,Juhani Junttila,Heikki Huikuri,Sirkka Keinänen-Kiukaanniemi,Kari Majamaa,Mika H. Martikainen

doi:10.1007/s00414-019-02091-4

Abstract

Cardiomyopathy and cardiac conduction defects are common manifestations of mitochondrial disease. Previous studies suggest that clinically asymptomatic individuals harbouring pathogenic mitochondrial DNA (mtDNA) mutations in the cardiac muscle may have sudden cardiac death (SCD) as the first manifestation of mitochondrial disease. We investigated the contribution of pathogenic mtDNA point mutations and mtDNA haplogroups in cardiac muscle in a cohort of 280 Finnish subjects that had died from non-ischaemic SCD with the median age of death at 59 years and in 537 population controls. We did not find any common or novel pathogenic mutations, but the frequency of haplogroup H1 was higher in the SCD subjects than that in 537 population controls (odds ratio: 1.76, confidence interval 95%: 1.02–3.04). We conclude that, at the population level, pathogenic point mutations in mtDNA do not contribute to non-ischaemic SCD, but natural variation may modify the risk.

Highlights

Sudden cardiac death (SCD) accounts for 15–20% of all deaths, and the population rates range between 50 and 100/ 100,000 [1]
The cardiac cause of death was confirmed in the autopsy and noncardiac sudden deaths were excluded, as were individuals who had a previous diagnosis of Coronary artery disease (CAD), or who were diagnosed with CAD based on autopsy findings
The m.3243A > G and m.3260A > G mutations were not detected in the cardiac tissue of 280 subjects that died from SCD

Summary

Introduction

Sudden cardiac death (SCD) accounts for 15–20% of all deaths, and the population rates range between 50 and 100/ 100,000 [1]. In the Finnish population, the annual incidence of SCD has been estimated to be 56.9/100,000 [2]. Int J Legal Med (2020) 134:39–44 third of non-ischaemic SCD events [2]. Among younger SCD subjects, monogenic disease leading to cardiomyopathy and various arrhythmias plays a major role [3]. Nonischaemic SCD, among young individuals, is etiologically multifactorial, and in many instances, no single causal factor can be confirmed with certainty [4]

Methods

Results

Conclusion