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Original Article
 

Associations With Aspirin-Intolerant Asthma in a Korean Population
 

J-H Kim,1 B-L Park,2 HS Cheong,2 CFA Pasaje,1 JS Bae,1 JS Park,3 AS Jang,3 S-T Uh,3 J-S Choi,4 Y-H Kim,4 M-K Kim,5 IS Choi,6 SH Cho,7 BW Choi,8 IS Koh,9 C-S Park,3 HD Shin1,2

1Department of Life Science, Sogang University, Seoul, Republic of Korea
2Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea
3Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
4Division of Allergy and Respiratory Disease, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
5Division of Internal Medicine, Chungbuk National University, Cheongju, Republic of Korea
6Department of Allergy, Chonnam National University, Gwangju, Republic of Korea
7Department of Internal Medicine and Institute of Allergy and Clinical Immunology, Seoul National University, Seoul, Republic of Korea
8Department of Internal Medicine, Chung-Ang University Yongsan Hospital, Seoul, Republic of Korea
9Department of Physiology, College of Medicine, Han Yang University, Seoul, Republic of Korea

J Investig Allergol Clin Immunol 2011; Vol. 21(5): 378-388
 

 Abstract


Background and objective: Lymphocyte-oriented kinase defi ciency encoded by the serine/threonine kinase 10 (STK10) gene correlates with the intracellular adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1) complex in aspirin hypersensitivity. This study investigated the association between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant asthma (AIA).

Methods: A total of 54 SNPs were genotyped in 163 AIA patients and 429 aspirin-tolerant asthma (ATA) controls.

Results: Logistic regression revealed that a synonymous variant (rs2306961G>A) had the most signifi cant association with AIA (P=.008 under the codominant model; P=.004 under the dominant model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT could play a role in regulating expression of STK10 in airway epithelium. Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is unique to rs2306961G>A, were significantly associated with aspirin hypersensitivity in asthmatics (P<.05).

Conclusions: Although replications in independent cohorts and further functional evaluations are needed, our preliminary fi ndings suggest that STK10 polymorphisms might be susceptible genetic markers of AIA and that gene expression could be mediated by tissue-specific codon usage.

Key words: Aspirin-intolerant asthma. STK10. Single-nucleotide polymorphism. Haplotype.