Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy

Eli F. Kelley, Troy J. Cross, Eric M. Snyder, Craig M. McDonald, Eric P. Hoffman, Luca Bello

Research output: Contribution to journalArticle

Abstract

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.

Original languageEnglish (US)
Article number221
JournalRespiratory Research
Volume20
Issue number1
DOIs
StatePublished - Oct 16 2019

Fingerprint

Duchenne Muscular Dystrophy
Adrenergic Receptors
Ventilation
Genotype
Prescriptions
Hypoventilation
Neuromuscular Diseases
Respiratory Muscles
Muscle Strength
Natural History
Proportional Hazards Models
Walking
Adrenal Cortex Hormones
Age Groups
Weights and Measures
Lung

Keywords

  • beta2-adrenergic receptor
  • Duchenne muscular dystrophy
  • Genotype
  • Nocturnal ventilation
  • Respiratory
  • Risk

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy. / Kelley, Eli F.; Cross, Troy J.; Snyder, Eric M.; McDonald, Craig M.; Hoffman, Eric P.; Bello, Luca.

In: Respiratory Research, Vol. 20, No. 1, 221, 16.10.2019.

Research output: Contribution to journalArticle

Kelley, Eli F. ; Cross, Troy J. ; Snyder, Eric M. ; McDonald, Craig M. ; Hoffman, Eric P. ; Bello, Luca. / Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy. In: Respiratory Research. 2019 ; Vol. 20, No. 1.
@article{98531c79a93144f88d83b5e320fe3b68,
title = "Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy",
abstract = "Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that {\ss}2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.",
keywords = "beta2-adrenergic receptor, Duchenne muscular dystrophy, Genotype, Nocturnal ventilation, Respiratory, Risk",
author = "Kelley, {Eli F.} and Cross, {Troy J.} and Snyder, {Eric M.} and McDonald, {Craig M.} and Hoffman, {Eric P.} and Luca Bello",
year = "2019",
month = "10",
day = "16",
doi = "10.1186/s12931-019-1200-1",
language = "English (US)",
volume = "20",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Influence of β2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy

AU - Kelley, Eli F.

AU - Cross, Troy J.

AU - Snyder, Eric M.

AU - McDonald, Craig M.

AU - Hoffman, Eric P.

AU - Bello, Luca

PY - 2019/10/16

Y1 - 2019/10/16

N2 - Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.

AB - Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.

KW - beta2-adrenergic receptor

KW - Duchenne muscular dystrophy

KW - Genotype

KW - Nocturnal ventilation

KW - Respiratory

KW - Risk

UR - http://www.scopus.com/inward/record.url?scp=85073451083&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073451083&partnerID=8YFLogxK

U2 - 10.1186/s12931-019-1200-1

DO - 10.1186/s12931-019-1200-1

M3 - Article

C2 - 31619245

AN - SCOPUS:85073451083

VL - 20

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

IS - 1

M1 - 221

ER -