Association of Four-locus Gene Interaction with Aspirin-intolerant Asthma in Korean Asthmatics
Aspirin-intolerant asthma (AIA), a major clinical presentation of aspirin hypersensitivity, affects 10% of adult asthmatics. The genetic risk factors involved in the susceptibility to AIA have recently been investigated, but multilocus single-nucleotide polymorphisms (SNPs) associated with this susceptibility has not been evaluated.
We examined 246 asthmatic patients: 94 having aspirin intolerance and 152 having aspirin tolerance. We selected 23 SNPs of 13 candidate genes and genotyped each SNP using a primer extension method. Multilocus genetic interactions were examined using multifactor dimensionality reduction (MDR) to test all multilocus SNP combinations to identify a useful SNP set for predicting the AIA phenotype.
We identified the best model using the MDR method, which consisted of a four-locus gene–gene interaction with 65.16% balanced accuracy and a cross-validation consistency of 70% in predicting AIA disease risk among asthmatic patients. This model included four SNPs such as B2ADR 46A>G, CCR3–520T>G, CysLTR1–634C>T, and FCER1B–109T>C.
These results suggest that a multilocus SNP acts in combination to influence the susceptibility to aspirin intolerance in asthmatics and could be a useful genetic marker for the diagnosis of AIA.
KeywordsAspirin-intolerant asthma multifactor dimensionality reduction single-nucleotide polymorphism multilocus gene interaction
adrenergic, beta-2-, receptor, surface
chemokine (C-C motif) receptor 3
cysteinyl leukotriene receptor 1
cysteinyl leukotriene receptor 2
Fc fragment of IgE, high affinity I, receptor for; beta polypeptide
leukotriene C4 synthase
nonsteroidal antiinflammatory drug
thromboxane A2 receptor
transforming growth factor, beta 1
tumor necrosis factor alpha
This study was supported by grants from the Basic Research Program of the Korea Science and Engineering Foundation (R01-2006-000-10775-0) and the Korea Health 21 R&D Project of the Ministry of Health and Welfare, Republic of Korea (A050571).