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). CONCLUSION:Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics.

authors

Park TJ,Kim JH,Bae JS,Park BL,Cheong HS,Chun JY,Lee JS,Kim JY,Pasaje CF,Cho SH,Uh ST,Kim MK,Choi IS,Koh IS,Park CS,Shin HD

doi

10.1159/000321267

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

395-402

issue

4

eissn

1018-2438

issn

1423-0097

pii

000321267

journal_volume

155

pub_type

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