Influence of Genetic variation of the β 2-Adrenergic receptor on lung diffusion in patients with cystic fibrosis

Brittany R. Traylor, Courtney M. Wheatley, Thomas T. Skrentny, William T. Foxx-Lupo, Hanna Phan, Asad E. Patanwala, Wayne J. Morgan, Cori L. Daines, Ryan Sprissler, Eric M. Snyder

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Rationale: Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β 2-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance (D M), pulmonary capillary blood volume (Vc), and peripheral oxygen saturation (SaO 2) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β 2-adrenergic receptor (ADRB2). Methods: To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 ± 7 vs. 24±4years; ht = 168 ± 8 vs. 174 ± 12 cm; wt = 64 ± 16 vs. 70 ± 13 kg; BMI = 23 ± 4 vs. 23±3 kg/m 2; FEV 1 = 72 ± 27 vs. 92 ± 12%pred; VO 2peak = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV 1 and VO 2peak, mean ± SD, for CF and healthy, respectively). The study involved measurement of DLCO, D M, V C and SaO 2 before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln 27Gln vs. Glu 27Glu/Gln 27Glu. Results: Within the healthy group, there were no differences in DLCO, D M, V C, D M/V C at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu 27Glu/Gln 27Glu group had higher D M/V C and SaO 2 when compared to the Gln 27Gln group at baseline (p < 0.05). Both genotype groups demonstrated a significant decline in V C and an improvement in D M/V C and SaO 2 in response to albuterol. Subjects with the Glu 27 genotype experienced a greater improvement in D M/V C with albuterol when compared to subjects homozygous for Gln at amino acid 27. Conclusion: These results suggest that there are differences in lung diffusion and peripheral SaO 2 according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype.

Original languageEnglish (US)
Pages (from-to)610-616
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
Volume24
Issue number5
DOIs
StatePublished - Oct 1 2011

Keywords

  • Cystic fibrosis
  • Genetics
  • Lung diffusion
  • Oxygen saturation
  • β-adrenergic

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Influence of Genetic variation of the β <sub>2</sub>-Adrenergic receptor on lung diffusion in patients with cystic fibrosis'. Together they form a unique fingerprint.

  • Cite this