open access

Vol 77, No 1 (2009)
ORIGINAL PAPERS
Published online: 2008-12-19
Submitted: 2013-02-22
Get Citation

Association of A/T polymorphism of the CHRM2 gene with bronchodilator response to ipratropium bromide in asthmatic children

Aleksandra Szczepankiewicz, Anna Bręborowicz, Paulina Sobkowiak, Lucyna Kramer, Anna Popiel
Pneumonol Alergol Pol 2009;77(1):5-10.

open access

Vol 77, No 1 (2009)
ORIGINAL PAPERS
Published online: 2008-12-19
Submitted: 2013-02-22

Abstract


Introduction: The aim of this study was to analyze the possible association of A/T polymorphism of the CHRM2 gene with asthma, and pharmacogenetic analysis of the polymorphism with bronchodilator response to ipratropium bromide, an anticholinergic drug used in asthma.
Material and methods: Analysis was performed in a group of 113 children diagnosed with bronchial asthma, and in a group of 123 healthy children from a control group. Moreover, in the group of 32 asthmatic children without concurrent treatment with long-acting β2-agonists, bronchodilator response to ipratropium bromide was evaluated by the spirometric lung function test. Genetic analysis was performed for A/T polymorphism (rs6962027) of the CHRM2 gene. Genotyping was done with the PCR-RFLP method. Statistical analysis was performed using Statistica v.7.1 software.
Results: No association of A/T polymorphism was found with asthma (p = 0.865 for genotypes and p = 0.782 for alleles). In the pharmacogenetic analysis, it was observed that patients carrying TT genotype of CHRM2 gene polymorphism demonstrated significantly poorer response to anticholinergic drug as compared to the patients with other genotypes for this polymorphism (p = 0.035).
Conclusions: We found that TT genotype in the CHRM2 gene was associated with poor bronchodilator response in asthmatic patients. The results should be analyzed carefully considering the small sample size and should be confirmed by other research groups.

Abstract


Introduction: The aim of this study was to analyze the possible association of A/T polymorphism of the CHRM2 gene with asthma, and pharmacogenetic analysis of the polymorphism with bronchodilator response to ipratropium bromide, an anticholinergic drug used in asthma.
Material and methods: Analysis was performed in a group of 113 children diagnosed with bronchial asthma, and in a group of 123 healthy children from a control group. Moreover, in the group of 32 asthmatic children without concurrent treatment with long-acting β2-agonists, bronchodilator response to ipratropium bromide was evaluated by the spirometric lung function test. Genetic analysis was performed for A/T polymorphism (rs6962027) of the CHRM2 gene. Genotyping was done with the PCR-RFLP method. Statistical analysis was performed using Statistica v.7.1 software.
Results: No association of A/T polymorphism was found with asthma (p = 0.865 for genotypes and p = 0.782 for alleles). In the pharmacogenetic analysis, it was observed that patients carrying TT genotype of CHRM2 gene polymorphism demonstrated significantly poorer response to anticholinergic drug as compared to the patients with other genotypes for this polymorphism (p = 0.035).
Conclusions: We found that TT genotype in the CHRM2 gene was associated with poor bronchodilator response in asthmatic patients. The results should be analyzed carefully considering the small sample size and should be confirmed by other research groups.
Get Citation

Keywords

ipratropium bromide; asthma; muscarinic type 2 receptor gene (CHRM2); polymorphism; bronchodilator response

About this article
Title

Association of A/T polymorphism of the CHRM2 gene with bronchodilator response to ipratropium bromide in asthmatic children

Journal

Advances in Respiratory Medicine

Issue

Vol 77, No 1 (2009)

Pages

5-10

Published online

2008-12-19

Bibliographic record

Pneumonol Alergol Pol 2009;77(1):5-10.

Keywords

ipratropium bromide
asthma
muscarinic type 2 receptor gene (CHRM2)
polymorphism
bronchodilator response

Authors

Aleksandra Szczepankiewicz
Anna Bręborowicz
Paulina Sobkowiak
Lucyna Kramer
Anna Popiel

References (18)
  1. Mak JC, Barnes PJ. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung. Am Rev Respir Dis. 1990; 141(6): 1559–1568.
  2. Makker HK, Holgate ST. The contribution of neurogenic reflexes to hypertonic saline-induced bronchoconstriction in asthma. J Allergy Clin Immunol. 1993; 92(1 Pt 1): 82–88.
  3. Schramm CM, Arjona NC, Grunstein MM. Role of muscarinic M2 receptors in regulating beta-adrenergic responsiveness in maturing rabbit airway smooth muscle. Am J Physiol. 1995; 269(6 Pt 1): L783–L790.
  4. Molfino NA, Slutsky AS, Julià-Serdà G, et al. Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects. Am Rev Respir Dis. 1993; 148(5): 1238–1243.
  5. Morrison JF, Pearson SB, Dean HG. Parasympathetic nervous system in nocturnal asthma. Br Med J (Clin Res Ed). 1988; 296(6634): 1427–1429.
  6. Fryer AD, Wills-Karp M. Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge. J Appl Physiol (1985). 1991; 71(6): 2255–2261.
  7. O'Connor BJ, Towse LJ, Barnes PJ. Prolonged effect of tiotropium bromide on methacholine-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1996; 154(4 Pt 1): 876–880.
  8. Gosens R, Zaagsma J, Meurs H, et al. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006; 7: 73.
  9. Barnes PJ, Barnes PJ. Corticosteroid resistance in airway disease. Proc Am Thorac Soc. 2004; 1(3): 264–268.
  10. Wjst M, Fischer G, Immervoll T, et al. A genome-wide search for linkage to asthma. German Asthma Genetics Group. Genomics. 1999; 58(1): 1–8.
  11. Daniels SE, Bhattacharrya S, James A, et al. A genome-wide search for quantitative trait loci underlying asthma. Nature. 1996; 383(6597): 247–250.
  12. Fenech AG, Billington CK, Swan C, et al. Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle. Am J Respir Cell Mol Biol. 2004; 30(5): 678–686.
  13. Minette PA, Lammers JW, Dixon CM, et al. A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects. J Appl Physiol (1985). 1989; 67(6): 2461–2465.
  14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215.
  15. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis. 1987; 136(1): 225–244.
  16. Society AT. Standarization of spirometry. Update. Am. J. Respir. Crit. Care Med. 1994; 152: 1107–1036.
  17. Yamamoto T, Yamashita N, Kuwabara M, et al. Mutation screening of the muscarinic m2 and m3 receptor genes in asthmatics, outgrow subjects, and normal controls. Ann Genet. 2002; 45(3): 109–113.
  18. Fenech AG, Ebejer MJ, Felice AE, et al. Mutation screening of the muscarinic M(2) and M(3) receptor genes in normal and asthmatic subjects. Br J Pharmacol. 2001; 133(1): 43–48.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Pneumonologia i Alergologia Polska dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl