Influence of beta(1) Adrenergic Receptor Genotype on Longitudinal Measures of Left Ventricular Ejection Fraction and Responsiveness to beta-Blocker Therapy in Patients With Duchenne Muscular Dystrophy

The purpose of this study was to determine whether the longitudinal progression of decline in left ventricular ejection fraction (LVEF) in Duchenne muscular dystrophy (DMD) patients is moderated by ADRB1 genotype and whether the efficacy of beta-blocker therapy is influenced by genotype status. About 147 DMD patients (6-34 years.) were analyzed with a focus on beta(1) adrenergic receptor (ADRB1) genotype variants. Patients were grouped by ADRB1 genotype resulting in Gly389 patients and Arg389 patients. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of LVEF across patient ages between genotype groups and for beta-blocker use. Both genotype groups displayed a progressive decline in LVEF starting around the mean age of ambulation loss (similar to 12 years). However, there was no difference between genotype groups in the progression of decline in LVEF. There was a significant effect of beta-blocker use on longitudinal LVEF, wherein patients on beta-blockers had systematically lower LVEF when compared to patients not on beta-blockers. However, the effect of beta-blocker therapy on LVEF was not affected by ADRB1 genotype. The current study did not demonstrate an influence of patient ADRB1 genotype on longitudinal LVEF in our cohort. Despite previous literature suggesting a positive influence of beta-blocker use on cardiac function in DMD patients and of an ADRB1 genotypic difference in responsiveness to beta-blocker use, we did not observe this in our cohort. Interestingly, our cohort did not demonstrate a positive influence of beta-blocker use on LVEF measures.