Email updates

Keep up to date with the latest news and content from BMC Pulmonary Medicine and BioMed Central.

Open Access Research article

Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis

Fernando A L Marson1*, Carmen S Bertuzzo2, Antônio F Ribeiro1 and José D Ribeiro1

Author Affiliations

1 Department of Pediatrics, School of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111, Campinas, SP, Brazil

2 Department of Genetics, Faculty of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111, Campinas, SP, Brazil

For all author emails, please log on.

BMC Pulmonary Medicine 2012, 12:50  doi:10.1186/1471-2466-12-50

Published: 5 September 2012

Abstract

Background

The most common cystic fibrosis (CF) manifestation is the progressive chronic obstructive pulmonary disease caused by deficiency, dysfunction, or absence of the CFTR (Cystic Fibrosis Transmembrane Regulator) protein on the apical surface of the cells in the respiratory tract. The use of bronchodilators (BD), and inhaled corticosteroids (IC) have been suggested for the management of airway inflammation in CF. The effectiveness of BD and IC have been verified, proven in laboratory and in the clinical treatment for asthma patients. However, in CF, the effectiveness of these drugs is controversial. The extent of asthma’s response to BD depends on the presence of polymorphisms in the ADRB2 gene. In contrast, in CF, little is known about the response to the BD and the association of CF´s severity with the different polymorphisms in ADRB2 gene. In this context, our objective was to verify whether the Arg16Gly and Glu27Gln polymorphisms in ADRB2 gene are associated with severity and with the bronchodilator response in CF patients.

Method

Cross-sectional study of 122 CF patients subjected to analysis of mutations in the CFTR gene, polymorphisms in ADRB2 gene, along with clinical and laboratorial characteristics of severity.

Result

The Arg16Gly polymorphism in ADRB2 gene was associated with pancreatic insufficiency(p:0.009), Bhalla score(p:0.039), forced expiratory volume in the first second[FEV1(%)](p:0.003), forced expiratory flow between 25 and 75% of the forced vital capacity-FVC[FEF25-75(%)](p:0.008) and lower age at the first isolation of the Pseudomonas aeruginosa(p:0.012). The response to the BD spirometry was associated with clinical severity markers, FEV1(%)(p:0.011) and FEF25-75(%)(p:0.019), for the Arg16Gly polymorphism in the ADRB2 gene. The haplotype analysis showed association with the FEV1/FVC marker from the spirometry test, before and after using the BD, with higher values in the group with Gly/Gly and Glu/Glu, respectively, for the Arg16Gly and Gln27Glu polymorphisms. The analysis by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly was respondent by 17.35% and Gln27Glu by 6.8% in variation found.

Conclusion

There was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.

Keywords:
Beta 2 adrenergic receptor; ADRB2 gene; Pulmonary function; Cystic fibrosis; Phenotype; Genotype