Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population

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.