Abstract
BACKGROUND: Sudden cardiac death (SCD) remains a major cause of death in Western countries. It has a heritable component, but previous molecular studies have mainly focused on common genetic variants. We studied the prevalence, clinical phenotypes, and risk of SCD presented by ten rare mutations previously associated with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, or catecholaminergic polymorphic ventricular tachycardia. METHODS: The occurrence of ten arrhythmia-associated mutations was determined in four large prospective population cohorts (FINRISK 1992, 1997, 2002, and Health 2000, n = 28,465) and two series of forensic autopsies (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 825). Follow-up data were collected from national registries. RESULTS: The ten mutations showed a combined prevalence of 79 per 10,000 individuals in Finland, and six of them showed remarkable geographic clustering. Of a total of 715 SCD cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W. CONCLUSIONS: Arrhythmia-associated mutations are prevalent in the general Finnish population but do not seem to present a major risk factor for SCD, at least during a mean of 10-year follow-up of a random adult population sample.