title: The association between the IL-4, ADRβ2 and ADAM 33 gene polymorphisms and asthma in the Taiwanese population.
abstract: BACKGROUND
  The association between genetic polymorphisms of ADRβ2, IL-4, and ADAM3 and asthma remains undetermined. Furthermore, it is not clear as to whether these three gene polymorphisms combined produce a correlative increase in asthmatic risk.
  
  
  METHODS
  A total of 476 asthmatic patients and 115 healthy volunteers were enrolled. Single nucleotide polymorphisms (SNPs) of the C-589T IL-4 promoter (rs2243250), the ADRβ2 gene [at nucleic acid 46 (rs1042713) and 79 (rs1042714)] and the ADAM33 gene [at rs2280091 (T1), rs3918396 (S1), rs3918391 (D1), and rs615436] were analyzed. Pulmonary function tests, methacholine challenge tests, total IgE, specific IgE for inhalant allergens and total eosinophil counts were assessed.
  
  
  RESULTS
  The T allele for the IL-4 gene promoter (C-589T locus), the C allele frequency for ADRβ2 (Gln27Glu locus), and the A allele for the ADAM33 gene (rs2280091, T1) were higher in asthma patients than in normal individuals. In asthmatic patients, the A allele of ADAM33 (rs2280091) was associated with higher eosinophil count and increased hyperresponsiveness compared to the C allele. Combination of the three risk genes SNP had an additive effect on the risk of asthma (OR: 3.46; CI: 1.51-7.93) and increased the diagnostic sensitivity and specificity of asthma.
  
  
  CONCLUSIONS
  Genetic polymorphism in the IL-4 promoter, ADRβ2, and ADAM33 is associated with asthma. Furthermore, ADAM33 genetic polymorphism modifies the phenotype of asthma in atopy and hyperresponsiveness. Asthma is a complex polygenic disease, and combinations of polymorphisms of various genes have an additive effect on the risk of asthma.
authors.affiliation: Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. chiang01@vghtpe.gov.tw
authors.forename: Chi-Huei
authors.initials: CH
authors.lastname: Chiang
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.forename: Ueng-Cheng
authors.initials: UC
authors.lastname: Yang
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
chemical_list: C508598:IL4 protein, human; D018343:Receptors, Adrenergic, beta-2; D015847:Interleukin-4; D051722:ADAM Proteins; C450441:ADAM33 protein, human