title: Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is characterized by the development of airway obstruction in asthmatic individuals following the ingestion of aspirin or other nonsteroidal anti-inflammatory drugs. TAPBP (TAP-binding protein, tapasin) is upregulated by eicosanoids, which act as potent inflammatory molecules in aspirin-related reactions. Thus, functional alterations in the TAPBP gene may contribute toward AERD.
  
  
  OBJECTIVE
  We examined the relationship between the single nucleotide polymorphisms on the TAPBP gene and AERD.
  
  
  METHODS
  A group of asthmatic patients (n=1252) underwent the oral aspirin challenge. Oral aspirin challenge reactions were categorized into two groups as follows: 15% or greater decreases in forced expiratory volume in 1 s or naso-ocular and skin reactions (AERD), or 15% or less decreases in forced expiratory volume in 1 s without naso-ocular and skin reactions (aspirin-tolerant asthma). Five single nucleotide polymorphisms of the TAPBP gene were genotyped.
  
  
  RESULTS
  Logistic regression analysis showed that the minor allele frequencies of TAPBP rs2071888 C>G (Thr260Arg) on exon 4 (P>0.05), which was in absolute linkage disequilibrium with rs1059288 T>C on 3'UTR, were significantly higher in the AERD group than in the aspirin-tolerant asthma group, and the P values remained significant after multiple comparisons (Pcorr=0.006, odds ratio: 1.37, 95% confidence interval: 1.11-1.69, additive model; Pcorr=0.009, odds ratio: 1.52, 95% confidence interval: 1.14-2.03, dominant model). Alpha-helical wheel plotting showed that 260Arg had greater hydrophilic helical property than 260Thr.
  
  
  CONCLUSIONS
  TAPBP polymorphisms may play a role in the development of AERD.
authors.affiliation: Department of Internal Medicine, Genome Research Center for Allergy and Respiratory Disease, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Sung-hwan
authors.initials: SH
authors.lastname: Cho
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Da-Jeong
authors.initials: DJ
authors.lastname: Bae
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D055963:Asthma, Aspirin-Induced / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D026901:Membrane Transport Proteins; C107762:tapasin; D001241:Aspirin