Association analysis of UBE3C polymorphisms in Korean aspirin-intolerant asthmatic patients

Abstract

Background: Aspirin-intolerant asthma (AIA), as an asthma phenotype that involves the upper or lower airways, occurs from excessive leukotriene production on administration of nonsteroidal anti-inflammatory drugs. The UBE3C gene on chromosome 7 is a member of the E3 ligase enzymes and is implicated in the ubiquitin-proteasome pathway. This pathway is involved in immune responses to inflammation, including asthma. Objective: To investigate whether the UBE3C polymorphisms are associated with the risk of AIA. Methods: Twenty-four nonmonomorphic genetic variants of UBE3C were genotyped in 163 patients with AIA and 429 controls with aspirin-tolerant asthma. After genotyping, logistic analyses were performed and haplotypes of each individual were inferred using the PHASE algorithm. Results: Logistic analyses revealed that 2 polymorphisms (rs3802122 and rs6979947) in the intron showed significant associations with risk of AIA (P < .001 and P-corr = .002 in both single nucleotide polymorphisms; odds ratios, 0.61 and 0.60, respectively). In associations with haplotypes, haplotype 2, which contains all the significantly associated single nucleotide polymorphisms and was infrequent in AIA compared with aspirin-tolerant asthma, was associated with aspirin hypersensitivity in asthmatic patients (P = .003 and P-corr = .03; odds ratio, 0.64; 95% confidence interval, 0.47-0.86). Conclusions: The rs3802122 and rs6979947 polymorphisms were significantly associated with the risk of AIA. However, further studies are required to establish the underlying mechanism by which UBE3C and its polymorphisms affect the risk of AIA. Ann Allergy Asthma Immunol. 2010;105:307-312.