title: Possible association of SLC22A2 polymorphisms with aspirin-intolerant asthma.
abstract: BACKGROUND
  Aspirin-intolerant asthma (AIA) is a clinical syndrome characterized by acute bronchoconstriction following the ingestion of aspirin. Solute carrier family 22, member 2 (SLC22A2), also known as organic cation transporter 2 (OCT2), is predominantly expressed in the luminal membrane of airway epithelial cells and has been shown to mediate the transport of prostaglandins on the cyclooxygenase pathway which is regulated by aspirin blockage. Recently, SLC22A2-mediated uptake inhibition by several nonsteroidal anti-inflammatory drugs and decreased SLC22A2 transport activity by its genetic variants have been elucidated in asthma.
  
  
  METHODS
  To investigate the associations between AIA and genetic polymorphisms of the SLC22A2 gene, 18 variants were genotyped in 163 AIA subjects and 429 aspirin-tolerant asthma (ATA) controls. Logistic analyses were used to evaluate p values for the associations of SLC22A2 polymorphisms with AIA.
  
  
  RESULTS
  One common polymorphism in intron 5, i.e. rs316021, was significantly associated with susceptibility to AIA (p = 0.004, P(corr) = 0.05, OR = 0.60, 95% CI = 0.43-0.85 in a codominant model). The minor allele frequency of rs316021 in the AIA group was significantly lower than that in the ATA controls. In addition, a polymorphism in intron 4 (rs3912161) and a haplotype (SLC22A2-ht3) showed significantly stronger association signals with the FEV(1) fall rate induced by aspirin provocation in AIA subjects compared with ATA controls (p = 0.004, P(corr) = 0.05).
  
  
  CONCLUSIONS
  Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Park
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Joon-Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Chun
authors.forename: Jin-Sol
authors.initials: JS
authors.lastname: Lee
authors.forename: Jason Yongha
authors.initials: JY
authors.lastname: Kim
authors.forename: Charisse Flerida
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Cho
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: In Song
authors.initials: IS
authors.lastname: Koh
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
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; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D001241:Aspirin