Possible Association of SLC22A2  Polymorphisms with Aspirin-Intolerant  Asthma

Possible Association of SLC22A2 Polymorphisms with Aspirin-Intolerant Asthma

  • نوع فایل : کتاب
  • زبان : انگلیسی
  • مؤلف : Tae-Joon Park a Jeong-Hyun Kim a Joon-Seol Bae a Byung-Lae Park b Hyun Sub Cheong b Ji-Yong Chun a Jin-Sol Lee a Jason Yongha Kim a Charisse Flerida
  • چاپ و سال / کشور: 2011

Description

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). Conclusion: Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics.
Int Arch Allergy Immunol 2011;155:395–402 Received: May 17, 2010 Accepted after revision: September 15, 2010 Published online: February 22, 2011
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