Heat shock protein 70 polymorphism in hypertrophic cardiomyopathy of South Indian cohort

Hypertrophic cardiomyopathy is a disease of the myocardium inherited in an autosomal dominant mode of inheritance exhibiting clinical variability resulting in disease heterogeneity. Mutations in sarcomeric genes are implicated in the disease causation. Modifier genes and environmental factors are known to influence the phenotypic expression and severity of the disease. One such modifier gene is Heat shock protein-70 (HSP) which also acts as a molecular chaperon and its role in cardioprotection is also well established by inhibiting apoptosis, a manifestation of cardiac hypertrophy. The present study aims to elucidate the role of Hsp-70 polymorphisms viz: HSP 70-1/+190G/C, HSP 70-2/+1267A/G, HSP 70-hom/+2437T/C. 100 control samples and 100 HCM patients were genotyped for the 3 polymorphic regions of HSP 70: by PCR based RFLP analysis. A statistical significant association was observed in HSP 70-1/+190G/C and HSP 70-2/+1267A/G with the risk allele being ‘C’ and ‘G’ allele respectively. This was further substantiated by a stronger Linkage disequilibrium and secondary mRNA structure prediction studies, where ‘C’ allele of Hsp 70-1 was found to have a stable structure compared to the wild type. The study clearly pinpoints to the role of heat shock proteins as modifiers in the inflammatory responses and hemodynamic compensatory mechanisms associated with HCM. The implication of Hsp in cardioprotection though well established seems to influence the progression and severity of the diseased phenotype by altered chaperoning, protein folding and regulation of transcription factors and ultimately apoptotic mechanisms associated with cardiac hypertrophy and remodeling in HCM.