|
|
|||||||||||||
|
|
||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers |
1 University of Dundee, United Kingdom
* To whom correspondence should be addressed. E-mail: b.j.lipworth{at}dundee.ac.uk.
Accepted 29 May 2006
| Abstract |
|---|
Background: The homozygous presence of the
arginine-16 variant of the
2-adrenoceptor gene,
ADRB2, reverses the benefits from the regular use of
short-acting
2-agonists in asthmatic adults as
compared to the homozygous glycine-16 genotype. We studied
the effect of this polymorphic variation on asthma
exacerbations in children and young adults, and its
relation to long-acting
2-agonists.
Method: Cross-sectional survey using electronic records, direct interviews, genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples for 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland over 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months.
Results: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines, when comparing the homozygous genotypes Arg/Arg vs Gly/Gly (OR 2.05, 95%CI = 1.19-3.53, p=0.010). This genotypic hazard was largely in the salmeterol-treated patients when comparing Arg/Arg16 vs Gly/Gly16 (OR = 3.40, 95% CI = 1.19-9.40, p=0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group.
Conclusions: The arginine 16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype-selective salmeterol induced down regulation and impaired receptor coupling, and associated subsensitivity of response.
Keywords: asthma, beta 2 agonist, polymorphism
This article has been cited by other articles:
![]() |
D. M. LANG New asthma guidelines emphasize control, regular monitoring Cleveland Clinic Journal of Medicine, September 1, 2008; 75(9): 641 - 653. [Abstract] [Full Text] [PDF] |
||||
![]() |
R H Green and I D Pavord Use of long-acting {beta}2 agonists in arginine-16 homozygous patients with asthma Thorax, June 1, 2008; 63(6): 568 - 569. [Full Text] [PDF] |
||||
![]() |
N. L Metzger, D. R Kockler, and L. A. H. Gravatt Confirmed {beta}16 Arg/Arg Polymorphism in a Patient with Uncontrolled Asthma Ann. Pharmacother., June 1, 2008; 42(6): 874 - 881. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Sabato, A.-M. Irani, B. L. Bukaveckas, L. B. Schwartz, D. S. Wilkinson, and A. Ferreira-Gonzalez A Simple and Rapid Genotyping Assay for Simultaneous Detection of Two ADRB2 Allelic Variants Using Fluorescence Resonance Energy Transfer Probes and Melting Curve Analysis J. Mol. Diagn., May 1, 2008; 10(3): 258 - 264. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Panebra, M. R. Schwarb, S. M. Swift, S. T. Weiss, E. R. Bleecker, G. A. Hawkins, and S. B. Liggett Variable-length poly-C tract polymorphisms of the {beta}2-adrenergic receptor 3'-UTR alter expression and agonist regulation Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L190 - L195. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. E. Moore Exploration of the {beta}2-adrenergic receptor regulatory regions: the next step in the holy grail of asthma pharmacogenetics research Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L187 - L189. [Full Text] [PDF] |
||||
![]() |
L. B. Ware Clinical Year in Review III: Asthma, Lung Transplantation, Cystic Fibrosis, Acute Respiratory Distress Syndrome Proceedings of the ATS, September 15, 2007; 4(6): 489 - 493. [Full Text] [PDF] |
||||
![]() |
M. E. Wechsler, J.-A. O. Shepard, and E. J. Mark Case 15-2007 -- A 20-Year-Old Woman with Asthma and Cardiorespiratory Arrest N. Engl. J. Med., May 17, 2007; 356(20): 2083 - 2091. [Full Text] [PDF] |
||||
![]() |
S B Liggett Genetic variability of the {beta}2 adrenergic receptor and asthma exacerbations. Thorax, November 1, 2006; 61(11): 925 - 927. [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | REGISTER |