title: Mutational analysis of mitochondrial DNA in Brugada syndrome.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Stocchi
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Polidori
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy. Electronic address: lucia.potenza@uniurb.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Potenza
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy.
authors.forename: Marco Bruno Luigi
authors.initials: MB
authors.lastname: Rocchi
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calcabrini
authors.affiliation: Complex Operative Unit of Cardiology (UOC),Santa Maria della Misericordia Hospital, Urbino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Busacca
authors.affiliation: ASUR Marche-Area Vasta 1, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Capalbo
authors.affiliation: Complex Operative Unit of Cardiology (UOC), IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Potenza
authors.affiliation: Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Amati
authors.affiliation: Complex Operative Unit of Cardiology (UOC), Polyclinic Tor Vergata, Rome, Italy.
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Mango
authors.affiliation: Complex Operative Unit of Cardiology (UOC), Polyclinic Tor Vergata, Rome, Italy; Department of System Medicine, University of Tor Vergata, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
authors.affiliation: Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy; St. Peter Fatebenefratelli Hospital, Rome, Italy; Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy.
authors.forename: Vilberto
authors.initials: V
authors.lastname: Stocchi
mesh_terms: D000328:Adult; D000368:Aged; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
keywords: Brugada syndrome; Risk stratification; Sequence analysis; mtDNA; mtSNPs