J Asthma Allergy Clin Immunol.  2003 Dec;23(4):800-809.

Leukotriene related gene polymorphisms in ASA-intolerant asthma: an association of 5-lipoxygenase haplotype

Affiliations
  • 1Department of Allergy and Rheumatology, Ajou University Hospital, Korea. mdcspark@unitel.co.kr
  • 2Department of Pulmonology, Ajou University Hospital, Korea.
  • 3Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Korea.
  • 4Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, Korea.
  • 5Department of Genetic Epidemiology, SNP Genetics, Inc., Korea.

Abstract

BACKGROUND AND OBJECTIVES
A recent study has demonstrated a possible involvement of leukotriene C4 synthase (LTC4S) gene polymorphism in ASA-intolerant asthma (AIA) in a Polish population, while no significances were noted in other populations. To investigate the role of genetic polymorphism in AIA development, we screened single nucleotide polymorphisms (SNPs) for the key enzymes involved in arachidonate metabolism, and cysteinyl leukotriene receptor 1 (CYSLTR1) in a larger scale of Korean population with AIA.
MATERIALS AND METHODS
93 AIA and 181 ASA-tolerant asthma (ATA) patients, and 123 normal controls (NC) were enrolled. Single base extension method was applied for genotyping of SNPs in 5-lipoxygenase (ALOX5, -1708G>A, 21C>T, 270G>A, 1728G>A), ALOX5 activating protein (FLAP, 218A>G), cyclooxygenase 2 (COX2, -162C>G, 10T>G, 228G>A), LTC4S (-444A>C), and CYSLTR1 (927T>C). Haplotype analyses for ALOX5 were performed as well. RESULTS: There were no significant differences in allele and genotype frequencies of the SNPs among the three groups (p>0.05). However, the frequency of ALOX5-ht1[G-C-G-A] containing genotype in the AIA group was significantly higher than those of the ATA group (p=0.01, OR =5.0, 95%CI=1.54-17.9) and the normal controls (p=0.03, OR=4.5, 95%CI=1.1-18.4) with a dominant model. CONCLUSION: These results suggest a lack of association between FLAP, COX2, LTC4S, and CYSLTR1 gene polymorphisms, and AIA phenotype in Korean population. However, a possible involvement of ALOX5-ht1[G-C-G-A] in AIA development was suggested.

Keyword

aspirin; asthma; single nucleotide polymorphism; 5-lipoxygenase; haplotypes

MeSH Terms

Alleles
Arachidonate 5-Lipoxygenase*
Aspirin
Asthma*
Cyclooxygenase 2
Genotype
Haplotypes*
Humans
Leukotriene C4
Metabolism
Phenotype
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Receptors, Leukotriene
Arachidonate 5-Lipoxygenase
Aspirin
Cyclooxygenase 2
Leukotriene C4
Receptors, Leukotriene
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