Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population.
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.
Kim
Seung-Hyun
SH
Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
Choi
Jeong-Hee
JH
Holloway
J W
JW
Suh
Chang-Hee
CH
Nahm
Dong-Ho
DH
Ha
Eun-Ho
EH
Park
Choon-Sik
CS
Park
Hae-Sim
HS
D058927:5-Lipoxygenase-Activating Proteins; D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014581:Urticaria / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D015289:Leukotrienes; D008565:Membrane Proteins; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D001241:Aspirin