Lack of an Association between a Newly Identified Promoter Polymorphism (-1702G > A) of the Leukotriene C4 Synthase Gene and Aspirin-Intolerant Asthma in a Korean Population

Lack of an Association between a Newly Identified Promoter Polymorphism (-1702G > A) of the Leukotriene C4 Synthase Gene and Aspirin-Intolerant Asthma in a Korean Population

JEONG-HEE CHOI, SEUNG-HYUN KIM,¹ JIN-SIK BAE,¹ HONG-LEI YU,¹ CHANG-HEE SUH,¹ DONG-HO NAHM¹ and HAE-SIM PARK¹

Department of Pulmonology and Allergies, Bundang Jesaeng General Hospital, Seongnam, Korea, and ¹Department of Allergies and Rheumatology, Ajou University School of Medicine, Suwon, Korea

Aspirin-intolerant asthma (AIA) is a distinct clinical syndrome that refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). It is widely recognized that increased cysteinyl leukotriene (cysLT) biosynthesis is associated with the development and progression of AIA. Leukotriene C4 synthase (LTC4S) is the terminal enzyme in cysLT production and is a strong candidate gene in the pathogenesis of aspirin-intolerant asthma (AIA). In this paper, we report a new single nucleotide polymorphism (SNP) of the LTC4S promoter, -1702G>A, in AIA patients and evaluate its genetic role in the association with the LTC4S -444 A>C polymorphism. We enrolled 110 AIA patients, 125 aspirin-tolerant asthma (ATA) patients, and 125 normal controls. SNP genotyping of the LTC4S-1702G>A and -444A>C polymorphisms was performed using SNP-IT™ assays. Haplotype analyses were performed using Haploview version 2.05, which is based on an estimation-maximization (EM) algorithm. There were no significant differences in the allele or genotype frequencies of the LTC4S-1702G>A and -444A>C polymorphisms among the three groups (p > 0.05), with no significant differences in the observed haplotype frequencies (p > 0.05). Moreover, no significant associations were found between the genotype of each SNP in AIA patients with the clinical characteristics, including a forced expiratory volume in one second (FEV₁) %, a provocation concentration of methacholine to induce more than 20% decrease of FEV₁ (PC₂₀) to methacholine, and serum total IgE levels (p > 0.05). These results indicate that there is no association between these two promoter polymorphisms of LTC4S and the phenotype of AIA in a Korean population.

keywords —— aspirin-intolerant asthma; genetic polymorphism; leukotriene C4 synthase

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Tohoku J. Exp. Med., 2006, 208, 49-56

Received September 22, 2005; revision accepted for publication October 19, 2005.
Correspondence: Dr. Hae-Sim Park, M.D., Ph.D., Professor, Department of Allergies and Rheumatology, Ajou University School of Medicine, Wonchondong San-5, Yongtonggu, Suwon 442-721, Korea.

e-mail: hspark@ajou.ac.kr