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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[FEV 1 (%)](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, FEV 1 (%)(p:0.011) and FEF25-75(%)(p:0.019), for the Arg16Gly polymorphism in the  ADRB2  gene. The haplotype analysis showed association with the FEV 1 /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.

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