Expression of Proto-oncogenes and Gene Mutation of Sarcomeric Proteins in Patients With Hypertrophic Cardiomyopathy

Abstract

Abstract —Several mutations of cardiac β-myosin heavy chain (β-MHC) gene were reported in patients with hypertrophic cardiomyopathy (HCM). Involvement of proto-oncogenes has been shown in the mechanism of experimental cardiac hypertrophy. This study sought to examine the effects of c-H- ras and c- myc expression in the steady-state myocardium on hypertrophic changes and to evaluate the possible interaction between β-MHC mutation and proto-oncogene expression in HCM. Endomyocardial biopsy was performed in 17 HCM patients (5 β-MHC mutations and 1 troponin T mutation) and 7 control subjects (no mutation). Reverse transcription–polymerase chain reaction analysis revealed c-H- ras expression in all members of both groups. Cardiomyocyte size was correlated with the expression level of c-H- ras ( P <0.001), and c-H- ras expression was upregulated in HCM patients ( P <0.01). HCM patients with a β-MHC mutation had the higher c-H- ras expression than did control subjects or patients without a mutation ( P <0.01). c- myc mRNA was expressed in 7 of 17 HCM patients but not in control subjects. Myocyte size was greater in c- myc –positive HCM patients than in control subjects and c- myc –negative HCM patients ( P <0.001 and P <0.05, respectively). The proto-oncogene expression did not affect clinical findings, myocardial fibrosis, or disarray. In conclusion, c-H- ras and c- myc expression in the steady-state myocardium may play a role in the hypertrophic mechanism in HCM. It is possible that β-MHC gene mutation has some effect on the regulation of proto-oncogene expression in HCM.