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Association of Four-locus Gene Interaction with Aspirin-intolerant Asthma in Korean Asthmatics

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Abstract

Introduction

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.

Discussion

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.

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Fig. 1
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Abbreviations

AIA:

aspirin-intolerant asthma

ATA:

aspirin-tolerant asthma

ALOX5:

arachidonate 5-lipoxygenase

B2ADR:

adrenergic, beta-2-, receptor, surface

CCR3:

chemokine (C-C motif) receptor 3

CysLTR1:

cysteinyl leukotriene receptor 1

CysLTR2:

cysteinyl leukotriene receptor 2

FCER1B:

Fc fragment of IgE, high affinity I, receptor for; beta polypeptide

IL10:

interleukin 10

IL13:

interleukin 13

IL18:

interleukin 18

LTC4S:

leukotriene C4 synthase

NSAID:

nonsteroidal antiinflammatory drug

SNP:

single-nucleotide polymorphism

TBXA2R:

thromboxane A2 receptor

TGFβ1:

transforming growth factor, beta 1

TNFα:

tumor necrosis factor alpha

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Acknowledgements

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).

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Authors and Affiliations

  1. Department of Allergy and Rheumatology, School of Medicine, Ajou University, San-5, Woncheondong, Youngtonggu, 442-721, Suwon, South Korea

    Seung-Hyun Kim, Bo-Young Cho, Hyun-Young Lee & Hae-Sim Park

  2. School of Information and Communication, Ajou University, Suwon, South Korea

    Hyun-Hwan Jeong, MyoungKi Kim & Kyubum Wee

  3. Department of Mathematics, Ajou University, Suwon, South Korea

    Jungseob Lee

Authors
  1. Seung-Hyun Kim
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  2. Hyun-Hwan Jeong
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Correspondence to Hae-Sim Park.

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Kim, SH., Jeong, HH., Cho, BY. et al. Association of Four-locus Gene Interaction with Aspirin-intolerant Asthma in Korean Asthmatics. J Clin Immunol 28, 336–342 (2008). https://doi.org/10.1007/s10875-008-9190-7

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  • DOI: https://doi.org/10.1007/s10875-008-9190-7

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