| Popis: |
Introduction Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia (ARVC/D) is a genetic disorder characterized by fibrofatty replacement of right ventricle. Extensive research revealed the involvement of desmosomal, non-desmosomal and modifier genes in the etiology of the ARVC/D. Further, environmental factors with modifier genes influence the severity of the disease. One of the well-known modifier genes is HSP90α polymorphism, which is involved in protein folding and regulation as well as apoptosis etc. Therefore, in this study, an investigation was carried out to find the possible association between HSP90α polymorphism and ARVC/D. Material and methods This study included 240 healthy control samples without any family history of cardiac diseases and 61 ARVC/D patients. Diagnosis of patients was carried out using ECG and 2-D echocardiography, following revised diagnostic criteria: definite, borderline diagnosis and possible diagnosis. Scoring of genotypes was carried out by allelic-specific PCR. Results A statistically significant association was observed between HSP90α polymorphism and ARVC/D. In codominant and overdominant models, ‘C/G’ was found to be risk conferring. Further, in dominant model, ‘C/G’ and ‘G/G’ genotypes were susceptible for ARVC/D. Moreover, ‘G’ allele which was predominant in ARVC/D was found to risk conferring towards ARVC/D. Conclusion These findings suggest that possible role ofHSP90α polymorphism in the etiology of ARVC/D. The ‘G’ allele of HSP90α polymorphism damages the 3-D native conformations, which is required for the interaction between client proteins such as desmosomes, ryanodine receptor-2 and sodium channel leading to mislocalization of these proteins. Furthermore, loss of inhibitory interaction between HSP90α protein and Apaf-1 trigger apoptosis. |
