The ACTN3 577XX null genotype is associated with low left ventricular dilation-free survival rate in patients with Duchenne muscular dystrophy: ACTN3 genotype relates cardiomyopathy in DMD

Abstract Background Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease caused by mutations in the DMD gene. Dilated cardiomyopathy is the leading cause of death in DMD; therefore, further understanding of this complication is essential to reduce morbidity and mortality. Methods A common null variant (R577X) in the ACTN3 gene, which encodes α-actinin-3, has been studied in association with muscle function in healthy individuals, however not yet examined with cardiac phenotype in DMD. Here, we determined the ACTN3 genotype in 163 Patients with DMD and examined the correlation between ACTN3 genotypes and echocardiographic findings in 77 of the 163 patients. Results The genotypes 577RR(RR), 577RX(RX), and 577XX(XX) were identified in 13 (17%), 44 (57%), and 20 (26%) of 77 patients, respectively. We estimated cardiac involvement-free survival rate analyses using Kaplan-Meier curves. Remarkably, the left ventricular (LV) dilation (LVDd>55 mm)-free survival rate was significantly lower in XX null genotype patients (P Conclusions This study revealed that ACTN3 XX null genotype was associated with a lower LV dilation-free survival rate in DMD. These results suggest that ACTN3 genotype should be determined at the time of diagnosis of DMD to improve patients’ cardiac outcomes.