title: CD53, a suppressor of inflammatory cytokine production, is associated with population asthma risk via the functional promoter polymorphism -1560 C>T.
abstract: BACKGROUND
  In this study, the association of asthma with CD53, a member of the tetraspanin family, was assessed for the first time in a mechanism-based study.
  
  
  METHODS
  Genetic polymorphisms of CD53 were analyzed in 591 subjects and confirmed in a replication study of 1001 subjects. CD53 mRNA and protein levels were measured in peripheral blood leukocytes, and the effects of the promoter polymorphisms on nuclear factor binding were examined by electrophoretic mobility shift assay. Cellular functional studies were conducted by siRNA transfections.
  
  
  RESULTS
  Among tagging SNPs of CD53, the -1560 C>T in the promoter region was significantly associated with asthma risk. Compared with the CC genotype, the CT and TT genotypes were associated with a higher asthma risk, with odd ratios of 1.74 (P=0.009) and 2.03 (P=0.004), respectively. These findings were confirmed in the replication study with odd ratios of 1.355 (P=0.047) and 1.495 (P=0.039), respectively. The -1560 C>T promoter SNP had functional effects on nuclear protein binding as well as mRNA and protein expression levels in peripheral blood leukocytes. When CD53 was knocked down by siRNA in THP-1 human monocytic cells stimulated with house dust mite, the production of inflammatory cytokines as well as NFκB activity was significantly over-activated, suggesting that CD53 suppresses over-activation of inflammatory responses.
  
  
  CONCLUSIONS
  The -1560 C>T SNP is a functional promoter polymorphism that is significantly associated with population asthma risk, and is thought to act by directly modulating nuclear protein binding, thereby altering the expression of CD53, a suppressor of inflammatory cytokine production.
authors: Department of Microbiology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors: Haeyong
authors: H
authors: Lee
authors: Sungmin
authors: S
authors: Bae
authors: Jaewoong
authors: J
authors: Jang
authors: Byoung Whui
authors: BW
authors: Choi
authors: Choon-Sik
authors: CS
authors: Park
authors: Jong Sook
authors: JS
authors: Park
authors: Seung-Hyo
authors: SH
authors: Lee
authors: Yoosik
authors: Y
authors: Yoon
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D039981:Pyroglyphidae / Q000276:immunology; D060265:Tetraspanin 25 / Q000235:genetics / Q000502:physiology*
chemical_list: C554894:CD53 protein, human; D016207:Cytokines; D060265:Tetraspanin 25