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Leukotriene C4 Synthase 유전자 Promoter 부위 유전적 다형과 아스피린 과민성 천식의 연관성
김상헌 ( Sang Heon Kim ),박흥우 ( Heung Woo Park ),손성욱 ( Seong Wook Sohn ),이상민 ( Sang Min Lee ),오선영 ( Sun Young Oh ),김선신 ( Sun Sin Kim ),박준우 ( Joon Woo Bahn ),장윤석 ( Yoon Seok Chang ),신은순 ( Eun Soon Shin ),이 대한천식알레르기학회 2006 천식 및 알레르기 Vol.26 No.2
Background: The 5-lipoxygenase, 5-lipoxygenase associated protein and leukotriene C4 (LTC4) synthase are enzymes involved in the synthesis of cysteinyl leukotrienes which are known to be important lipid mediators for the development of aspirin-intolerant asthma (AIA). Several studies have evaluated genetic association between polymorphisms of these enzymes and AIA, reporting inconsistent results. Objective: To evaluate the genetic effect of polymorphisms of promoter areas of ALOX5, ALOX5AP and LTC4S genes in the development of AIA. Method: Polymorphisms in promoter areas of ALOX5 (-1761G>A, -1708G>A), ALOX5AP (21A/18A repeat) and LTC4S (-444A>C) were genotyped in patients with AIA (n=44), aspirin-tolerant asthma (ATA, n=104), and healthy-normal controls (NC, n=107). Result: The frequency of LTC4S -444 AC or CC alleles was significantly lower in AIA patients than in ATA patients (19.0% vs. 36.5%, P=0.005, OR=0.23, 95%CI 0.08∼0.64). However, the frequency of these genotypes was not different between AIA and NC (19.0% vs. 24.8%, P=0.458). As to LOX5 -1761G>A, -1708G>A, and ALOX5AP 21A/18A repeat, the frequency of these genotypes was not different between AIA and ATA patients and between AIA and NC. Conclusion: A significant association was found between LTC4S -444A>C and the frequency of AIA. This finding suggests that LTC4 synthase may be involved in the development of AIA in the Korean population. (Korean J Asthma Allergy Clin Immunol 2006;26:115-121)