Stocchi Laura, Polidori Emanuela, Potenza Lucia, Rocchi Marco Bruno Luigi, Calcabrini Cinzia, Busacca Paolo, Capalbo Maria, Potenza Domenico, Amati Francesca, Mango Ruggiero, Romeo Francesco, Novelli Giuseppe, Stocchi Vilberto
Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Italy.
Cardiovasc Pathol. 2016 Jan-Feb;25(1):47-54. doi: 10.1016/j.carpath.2015.10.001. Epub 2015 Oct 22.
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.
Brugada综合征（BrS）是一种原发性电疾病，与因室颤导致的心源性猝死风险增加相关。这种病症有核基因异质性起源，目前，针对核DNA的分子诊断测试仅覆盖30%的BrS患者。本研究的目的是评估线粒体（mt）DNA变异在BrS中可能的作用，因为其在几种心肌病中的病因学作用已被描述。
对BrS患者的整个mt基因组进行测序和分析。可以排除导致BrS的特定mtDNA突变，但发现BrS患者的d环比对照病例的d环多态性更高（P = 0.003）。此外，变异数量最多（n>20）的患者与四个mt单核苷酸多态性（SNP）（T4216C、A11251G、C15452A、T16126C）以及最严重的BrS表型之间似乎存在关联（P = 0.002）。
在BrS患者mtDNA中发现的高替换率不太可能是该疾病的主要原因，但它可能是BrS表型表现的一个重要辅助因素。有证据表明特定的mtDNA等位基因组合和大量的mtDNA SNP可能与更严重的BrS病例相关，这代表了进一步队列研究的起点，旨在测试这种mt遗传状况是否可能是BrS临床表型的遗传调节因子。
