title: Relationship between polymorphisms in the 5' leader cistron, positions 16 and 27 of the adrenergic β2 receptor gene and asthma in a Han population from southwest China.
abstract: OBJECTIVE
  Adrenergic β2 receptors (ADRB2) play an important role in regulating pulmonary function. Many previous studies have investigated possible associations between polymorphisms in the ADRB2 gene and asthma, but have yielded conflicting results. Furthermore, little is known regarding the possible role of the Arg19Cys polymorphism in susceptibility to asthma among Chinese.
  
  
  METHODS
  This case-control association study involved 238 patients with asthma and 265 healthy subjects from a Han population in southwest China. For all subjects, the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene were characterized by direct sequencing. Genotype, allele and haplotype frequencies were determined. In addition, to evaluate the association between the ADRB2 polymorphisms and lung function, bronchodilator response to inhaled β2 agonists (400 µg of albuterol) was assessed in the asthmatic patients.
  
  
  RESULTS
  There were no significant differences in genotype or allele frequencies for the three ADRB2 polymorphisms between the two cohorts. The Arg19/Arg16/Gln27 haplotype was more frequent among asthmatic patients than control subjects (odds ratio 2.24, 95% confidence interval (CI): 1.05-4.73, P=0.04). Moreover, the Arg19/Cys19 genotype was associated with a lower FEV₁% (mean difference -4.5, 95% CI: -12.5 to 3.6, P=0.02) and FEV₁/FVC (mean difference 8.9, 95% CI: 8.5-9.4, P=0.01). The bronchodilator response to albuterol was also marginally lower in individuals who were homozygous for the Arg19 genotype (mean difference 4.2, 95% CI: 3.7-4.8, P=0.03).
  
  
  CONCLUSIONS
  The Arg19/Cys19 genotype was an independent risk factor for lower FEV₁% and FEV₁/FVC. Asthmatic patients with the Arg19/Arg19 genotype showed decreased responsiveness to albuterol. Furthermore, the Arg19/Arg16/Gln27 haplotype may contribute to increased susceptibility to asthma in the Chinese population.
authors.affiliation: Department of Respiratory Critical Care Medicine, The First Affiliated Hospital of Kunming Medical College, Chinese Academy of Sciences, Kunming, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Fu
authors.forename: Zhi-Huan
authors.initials: ZH
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.forename: Chang
authors.initials: C
authors.lastname: Sun
authors.forename: Li-Zhou
authors.initials: LZ
authors.lastname: Fang
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jing-Kui
authors.initials: JK
authors.lastname: Shu
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Lu-Ming
authors.initials: LM
authors.lastname: Dai
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000420:Albuterol / Q000627:therapeutic use; D001120:Arginine; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005541:Forced Expiratory Volume; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D005973:Glutamine; D001120:Arginine; D000420:Albuterol