Mutational analysis of mitochondrial DNA in Brugada syndrome

• DOI: 10.1016/j.carpath.2015.10.001
• Publication Date: 2015-10-25T11:37:29Z
• Authors: Laura Stocchi; Emanuela Polidori; Lucia Potenza; Marco Bruno Luigi...; Cinzia Calcabrini; Paolo Busacca; Maria Capalbo; Domenico Potenza; Francesca Amati; Ruggiero Mango; Francesco Romeo; Giuseppe Novelli; Vilberto Stocchi
• Keywords: Adult; Male; DNA Mutational Analysis; 610; Settore MED/03 - GENETICA MEDICA; DNA, Mitochondrial; Polymorphism, Single Nucleotide; Severity of Illness Index; mtSNPs; Electrocardiography; Young Adult; Brugada syndrome; mtDNA; mtSNPs; Risk stratification; Sequence analysis; Adult; Aged; Brugada Syndrome; Case-Control Studies; DNA, Mitochondrial; Electrocardiography; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Phenotype; Severity of Illness Index; Young Adult; DNA Mutational Analysis; Mutation; Polymorphism, Single Nucleotide; Cardiology and Cardiovascular Medicine; 2734; Brugada syndrome; Risk stratification; Sequence analysis; mtDNA; mtSNPs.; Humans; Brugada syndrome; Genetic Predisposition to Disease; Sequence analysi; Risk stratification; Genetic Association Studies; Aged; Brugada Syndrome; mtDNA; Middle Aged; 3. Good health; Phenotype; Case-Control Studies; Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE; Mutation; Female

Brugada syndrome (BrS) is a primary electrical disease associated with an increased risk of sudden cardiac death due to ventricular fibrillation. This pathology has nuclear heterogeneous genetic origins, and at present, molecular diagnostic tests on nuclear DNA cover only 30% of BrS patients. The aim of this study was to assess the possible involvement of mitochondrial (mt) DNA variants in BrS since their etiological role in several cardiomyopathies has already been described.The whole mt genome of BrS patients was sequenced and analyzed. A specific mtDNA mutation responsible for BrS can be excluded, but BrS patient d-loop was found to be more polymorphic than that of control cases (P=0.003). Moreover, there appears to be an association between patients with the highest number of variants (n>20) and four mt Single Nucleotide Polymorphism (SNPs) (T4216C, A11251G, C15452A, T16126C) and the most severe BrS phenotype (P=0.002).The high substitution rate found in BrS patient mtDNA is unlikely to be the primary cause of the disease, but it could represent an important cofactor in the manifestation of the BrS phenotype. Evidence suggesting that a specific mtDNA allelic combination and a high number of mtDNA SNPs may be associated with more severe cases of BrS represents the starting point for further cohort studies aiming to test whether this mt genetic condition could be a genetic modulator of the BrS clinical phenotype.