Genetic variations involved in sudden cardiac death and their associations and interactions

Abstract

Although the mechanism of sudden cardiac death (SCD) in heart failure is not completely known, genetic variations are known to play key roles in this process. Increasing numbers of mutations and variants are being discovered through genome-wide association studies. The genetic variations involved in the mechanisms of SCD have aroused widespread concern. Comprehensive understanding of the genetic variations involved in SCD may help prevent it. To this end, we briefly reviewed the genetic variations involved in SCD and their associations and interactions, and observed that cardiac ion channels are the core molecules involved in this process. Genetic variations involved in cardiac structure, cardiogenesis and development, cell division and differentiation, and DNA replication and transcription are all speculated to be loci involved in SCD. Additionally, the systems involved in neurohumoral regulation as well as substance and energy metabolism are also potentially responsible for susceptibility to SCD. They form an elaborate network and mutually interact with each other to govern the fate of SCD-susceptible individuals.

(Re-)programming of subtype specific cardiomyocytes

“…Exemplifying this, smoking-associated cardiac defects have been linked to promotor DNA hypermethylation of Tbx5 and Gata4 caused by maternal nicotine exposure [87]. In contrast, mutations in genes encoding cardiac ion channels are largely associated with phenotypes associated with sudden cardiac death (SCD) resulting from lethal arrhythmias [88].…”

The role of the sympathetic nervous system in sudden cardiac death

“…Lifethreatening arrhythmias, which can lead to SCD, are also known to be associated with electrolyte imbalances, such as hypokalemia, but also hyperkalemia and hypomagnesemia, metabolic abnormalities, severe inflammation and endocrine disorders (hyper-and hypothyroidism) (3). More recently, several genetic variations, including those affecting ion channels, cardiac structural proteins, cardiogenesis, cardiac development, energy metabolism and genes related to neurohormal regulation, have been implicated in development of SCD (11). One of the proposed and, possibly unifying mechanism, is the attribution of SCD to the sympathetic stress response (1).…”

“…Aside from drugs modulating ion channels and drugs affecting the renin-angiotensin system, typical therapy of high-risk patients involves the use of drugs (ß-adrenoceptor blockers) that oppose the effects of catecholamines as well as the implantation of cardioverter defibrillators (1,8). Both the pathogenesis and the prevention/treatment of SCD have been extensively reviewed in the recent literature (9)(10)(11)(12)(13)(14) and, based on these, the American College of Cardiology (ACC)/American Heart Association (AHA) as well as European Society of Cardiology (ESC) have updated their guidelines regarding this topic. The purpose of the present article is to briefly discuss the underlying etiologies, risk stratification methods and treatment strategies for SCD, and provide a detailed assessment of the mechanisms associated with SCD, mainly the release and subsequent oxidation of excessive catecholamines through the sympathetic stress response.…”

Diagnostic’s experience and ten-year tretment outcomes of patients with brugada syndrome

“…населения в год [1]. По данным разных исследо-ваний, в 65-85% случаев ВСС регистрируется у лиц с сохранной контрактильной функцией левого желудочка в отсутствие воспалительных или ишемических поражений миокарда, что за-трудняет диагностику и проведение мероприя-тий по предупреждению ВСС у этой группы больных [2]. Непосредственной причиной ВСС в таких случаях чаще всего являются жизнеугро-жающие желудочковые аритмии, которые могут иметь наследственную природу, что означает риск развития фатальных аритмий не только у больного, но и у его детей и близких родствен-ников.…”