Objective: Duchenne muscular dystrophy (DMD) is an inherited x-link disease caused by the deletion of the dystrophin gene. DMD is characterized by progressive muscle weakness and degeneration of skeletal, cardiac and respiratory muscles resulting in severe functional impairment. The beta-2 adrenergic receptor (ADRB2) plays a functional role in muscle size, strength and regeneration through regulation of multiple downstream mechanisms. Multiple polymorphisms of the ADRB2 have been identified as including a glycine (Gly) for arginine (Arg) substitution at amino acid 16. This polymorphism (Gly16) has been shown to have higher receptor density on lymphocytes, be more resistant to receptor down regulation, and have improved lung function. The objective of this study was to determine the influence, if any, of ADRB2 genotype on body composition and cardiopulmonary health outcomes in DMD. Methods: Nineteen patients were recruited through the University of Minnesota Fairview Clinic. DNA was collected via buccal swabs and analyzed for ADRB2 genotype. Medical records were then accessed to obtain retrospective data on age of loss of ambulation and start of corticosteroid treatment, DEXA, and cardiopulmonary measures when available. Results: There were no differences between genotype groups in age of loss of ambulation (AMB) or start of corticosteroid treatment (STER) (AMB = 11.3 ± 1.09, 12 ± 0.71, STER = 8.67 ± 3.68, 7.22 ± 2.23 for Arg and Gly respectively). Additionally, there were no differences between genotype groups in age, height, weight, BMI, or BSA (age = 11.9 ± 4.1, 11.3 ± 3.5, height = 140.8 ± 18.7, 143.1 ± 19.7, weight = 47.7 ± 22.8, 45.7 ± 19.3, BMI = 23.6 ± 18.6, 21.5 ± 5.5, and BSA = 1.3 ± 0.39, 1.3 ± 0.33 for Arg and Gly respectively). Further, there were no differences between genotype groups in L1-L4, TBD, LBM, or LBM/BSA (L1-L4 = 0.66 ± 0.13, 0.69 ± 0.09, TBD = 0.69 ± 0.12, 0.64 ± 0.01, LBM = 62.6 ± 16.1, 65.5 ± 17.1, and LBM/BSA = 56.1 ± 29.6, 65.5 ± 17.1 for Arg and Gly respectively). There was a statistically significant difference between genotype groups for FEFmax at the patients’ youngest age (FEFmax = 77.1 ± 14.1, 97.4 ± 16.9 for Arg and Gly respectively). There may also have been a clinically significant difference between genotype groups for FVC and FEV1 at the patients’ youngest age (FVC = 85.1 ± 18.5, 94.5 ± 15.7, and FEV1 = 84.7 ± 16.1, 99.1 ± 18.9 for Arg and Gly respectively). However, there were no differences between genotype groups for FEFmax, FVC, and FEV1 at the patients’ mid-point and oldest age nor were there differences for MEP and MIP at any age. Furthermore, there were no differences between genotype groups for any of the cardiac measures at any age. Discussion: These data suggest the ADRB2 may play a role in an improved functional pulmonary capacity but does not influence body composition or cardiac measures. This suggests early intervention with ADRB2 treatment may serve to preserve functional pulmonary capacity and health outcomes in DMD.
University of Minnesota M.S. thesis. January 2017. Major: Kinesiology. Advisor: Eric Snyder. 1 computer file (PDF); vii, 52 pages.
The Effects Of Beta2-Adrenergic Receptor Genotype On Cardiopulmonary And Body Composition Measures In Duchenne Muscular Dystrophy.
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