Influence of β2 adrenergic receptor genotype on longitudinal measures of forced vital capacity in patients with Duchenne muscular dystrophy

• Published in: Neuromuscular disorders : NMD 2022-02, Vol.32 (2), p.150-158
• Main Authors: Kelley, Eli F, Cross, Troy J, McDonald, Craig M., Hoffman, Eric P., Bello, Luca
• Format: Article
• Language: English
• Subjects: Beta2-adrenergic receptor; Duchenne muscular dystrophy; Forced vital capacity; Genotype; Respiratory
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2021.12.006

•Gly16 patients had lower FVC%p values compared with the Arg16 patients.•The Gly16 polymorphism may be detrimental to respiratory function in DMD patients.•The variability of respiratory interventions may confound these results.•ADRB2 genotyping should be considered in the clinical management of DMD patients.•These findings are preliminary in nature and replication studies are needed. The progression of decline in forced vital capacity as percent predicated (FVC%p) is a strong indicator of worsening prognosis in patients with Duchenne muscular dystrophy (DMD). Evidence suggests that ß2 adrenergic (ADRB2) receptors may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function. The purpose of this study was to determine the influence of ADRB2 genotype on longitudinal measures of FVC%p as a function of age in DMD patients. Data from the CINRG Duchenne Natural History Study including 169 DMD patients (5–25 yrs) were analyzed. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of FVC%p across patient ages between genotype groups after controlling for patient demographics, corticosteroid-use, and ambulatory status. Both genotype groups displayed a progressive, maturational decline in FVC%p. Notwithstanding this decline, patients expressing the Gly16 polymorphism demonstrated systematically lower FVC%p values at any given age compared with patients expressing the Arg16 polymorphism (P < 0.01). Therefore, expressing the Gly16 polymorphism may prove detrimental to respiratory function in DMD patients. These data suggest maybe ADRB2 genotyping should be considered in the clinical management of DMD patients.