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Journal of Clinical Immunology

, Volume 28, Issue 4, pp 336–342 | Cite as

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

  • Seung-Hyun Kim
  • Hyun-Hwan Jeong
  • Bo-Young Cho
  • MyoungKi Kim
  • Hyun-Young Lee
  • Jungseob Lee
  • Kyubum Wee
  • Hae-Sim Park
Article

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.

Keywords

Aspirin-intolerant asthma multifactor dimensionality reduction single-nucleotide polymorphism multilocus gene interaction 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Seung-Hyun Kim
    • 1
  • Hyun-Hwan Jeong
    • 2
  • Bo-Young Cho
    • 1
  • MyoungKi Kim
    • 2
  • Hyun-Young Lee
    • 1
  • Jungseob Lee
    • 3
  • Kyubum Wee
    • 2
  • Hae-Sim Park
    • 1
  1. 1.Department of Allergy and Rheumatology, School of MedicineAjou UniversitySuwonSouth Korea
  2. 2.School of Information and CommunicationAjou UniversitySuwonSouth Korea
  3. 3.Department of MathematicsAjou UniversitySuwonSouth Korea

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