title: Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis.
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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  There was an association between the Arg16Gly and Gln27Glu polymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.
authors.affiliation: Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil. fernandolimamarson@hotmail.com
authors.forename: Fernando A L
authors.initials: FA
authors.lastname: Marson
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Bertuzzo
authors.forename: Antônio F
authors.initials: AF
authors.lastname: Ribeiro
authors.forename: José D
authors.initials: JD
authors.lastname: Ribeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012720:Severity of Illness Index; D013147:Spirometry; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C553443:ADRB2 protein, human; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator