Association of four-locus gene interaction with aspirin-intolerant asthma in Korean asthmatics.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kim
Seung-Hyun
SH
Department of Allergy and Rheumatology, School of Medicine, Ajou University, San-5, Woncheondong, Youngtonggu, 442-721 Suwon, South Korea.
Jeong
Hyun-Hwan
HH
Cho
Bo-Young
BY
Kim
Myoungki
M
Lee
Hyun-Young
HY
Lee
Jungseob
J
Wee
Kyubum
K
Park
Hae-Sim
HS
D000328:Adult; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008297:Male; D011014:Pneumonia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018077:Receptors, Leukotriene / Q000235:genetics
D018077:Receptors, Leukotriene; D001241:Aspirin