J Korean Med Sci.  2005 Dec;20(6):926-931. 10.3346/jkms.2005.20.6.926.

Leukotriene-related Gene Polymorphisms in Patients with Aspirin-intolerant Urticaria and Aspirin-intolerant Asthma: Differing Contributions of ALOX5 Polymorphism in Korean Population

Affiliations
  • 1Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea. hspark@ajou.ac.kr
  • 2Human Genetics Division, University of Southampton School of Medicine, Southampton, U.K.
  • 3Department of Statistics, Yonsei University, Seoul, Korea.
  • 4Asthma Genome Research Center, Soonchunhyang University, Bucheon, Korea.

Abstract

The pathogenesis of aspirin (acetylsalicylic acid, ASA)-intolerant urticaria (AIU) is still poorly understood but it has recently been suggested that it is associated with the overproduction of leukotriene (LT). This is supported by evidence that cyclooxygenase 2 inhibitor is given safely to patients with AIU. The present study was designed to investigate the role of genetic polymorphism of LT related genes in the pathogenesis of AIU via a case-control study. We screened single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in leukotriene synthesis in the Korean population with AIU (n=101), ASA-intolerant asthma (AIA, n=95) and normal healthy controls (n=123). Genotype was determined by primer extension reactions using the SNapShot ddNTP primer extension kit. Among 8 SNPs of four LT related genes, the polymorphism of ALOX5 at positions of -1708 G>A showed significant difference in genotype frequency between AIU and AIA (p=0.01). Furthermore, there were significant differences observed in the frequencies of two ALOX5 haplotypes between the AIU group and AIA group (p<0.05). However, there were no differences in allele, genotype, or haplotype frequencies of ALOX5 between the AIU group and the normal control group. These results suggested that ALOX5 has a differing contribution in two major clinical pathogenesis related to ASA-sensitivity.

Keyword

Aspirin, Hypersensitivity; Urticaria; Polymorphism, Genetic; Leukotrienes

MeSH Terms

Adult
Arachidonate 5-Lipoxygenase/*genetics
Aspirin/*adverse effects
Asthma/etiology/*genetics/metabolism
Carrier Proteins/genetics
Case-Control Studies
Cyclooxygenase 2/genetics
Female
Gene Frequency
Genotype
Glutathione Transferase/genetics
Humans
Leukotrienes/*biosynthesis
Male
Membrane Proteins/genetics
Middle Aged
Polymorphism, Single Nucleotide
Research Support, Non-U.S. Gov't
Urticaria/etiology/*genetics/metabolism

Cited by  1 articles

Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease
Jong-Uk Lee, Jong Sook Park, Hun Soo Chang, Choon-Sik Park
Allergy Asthma Immunol Res. 2019;11(6):779-794.    doi: 10.4168/aair.2019.11.6.779.


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