IMPLICATION OF HSP70 GENE POLYMORPHISMS IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY/DYSPLASIA

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC/D) is characterized by initial fibrofatty replacement of the right ventricular. Mutations in the Desmosomal, non desmosomal apart from modifier genes are known to be involved in the pathogenesis of the ARVC/D. One such modifier gene identified is HSP70 which plays an important role in cardio-protection. The present study investigates the role of Hsp70 polymorphisms in ARVC/D disease severity. Methods: Analysis of 100 control samples and 33 ARVC/D patients for 3 polymorphic loci was carried out by PCR - RFLP. Statistical analysis was carried out by SNPSTAT and haploview to analyze and visualize LD. Results: Our study revealed a statistically significant association of HSP 70-1 +190 G/C [OR-3.01 (1.11-8.21)] and HSP 70-hom + 2437T/C [OR-3.08 (1.06-8.90)] genotypes with ARVC/D group. The haplotype frequency of CGT was also found to be higher in patients compared to controls, strengthening the synergistic effect of HSP70 family in ARVC/D. Conclusions: The present investigation revealed the importance of HSP70 polymorphisms in the pathogenesis of the ARVC/D. The inability HSP 70-1 polymorphism to perform its regular role may lead inflammation and apoptosis; whereas HSP 70-hom polymorphism confers a protective role by inhibiting the activation of NF-κB.