title: TNF-alpha (-308 G/A) and CD14 (-159T/C) polymorphisms in the bronchial responsiveness of Korean children with asthma.
abstract: BACKGROUND
  TNF-alpha is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-alpha gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated by CD14(+) cells.
  
  
  OBJECTIVE
  We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism and examined the combined effect with CD14 (-159T/C) polymorphism in Korean children.
  
  
  METHODS
  Asthmatic (n = 788) and control (n = 153) children were evaluated for asthma phenotypes. Genotypes were determined by using the single-base extension method and PCR-restriction fragment length polymorphism.
  
  
  RESULTS
  There was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C). Significantly lower PC(20) values were seen in asthmatic (P = .016) children with the TNF-alpha risk allele (-308A). Higher frequencies of 1 or 2 copies of the risk allele were found in asthmatic children with moderate-to-severe BHR to methacholine and exercise compared with control children (adjusted odds ratio of 2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20], respectively). In addition, asthmatic children with risk alleles at both loci had significantly greater BHR than those homozygous for the common alleles (P = .018).
  
  
  CONCLUSIONS
  The TNF-alpha promoter polymorphism (-308G/A) might be associated with severe BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-alpha promoter (-308A) and CD14 promoter (-159C) polymorphisms in terms of BHR.
  
  
  CONCLUSIONS
  The TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene.
authors.affiliation: Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Hyo-Bin
authors.initials: HB
authors.lastname: Kim
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Kang
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Ja-Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Bong-Seong
authors.initials: BS
authors.lastname: Kim
authors.forename: Seong-Ok
authors.initials: SO
authors.lastname: Jang
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha