Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma
Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma
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DOI：
10.1067/mai.2002.124466
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发表时间：
2002-06-01
影响因子：
14.2
通讯作者：
Akiyama, K
中科院分区：
文献类型：
--
作者：
Kawagishi, Y;Mita, H;Akiyama, K
背景资料：白三烯C-4合酶（LTC 4S）基因启动子区A → C颠换与阿司匹林诱导的哮喘（AIA）的发生有关。目的：研究日本人群LTC 4S基因多态性的频率及其与临床特征和半胱氨酰白三烯产生的关系。对60例AIA患者、100例阿司匹林耐受性哮喘（ATA）患者和110例对照者进行LTC 4S基因启动子分型。我们评估了基础水平的尿LTE 4，增加尿LTE 4静脉阿司匹林的挑战，和LTC 4S活性在外周血嗜酸性粒细胞。结果：变异C等位基因的频率是显着较高的AIA患者（等位基因频率[q] = 0.192）比ATA患者（q = 0.110，P = 0.042）。变异C等位基因携带者发生哮喘的年龄（31.8 +/- 2.9岁[平均值+/- SEM]）明显小于野生型A纯合子（41.3 +/- 2.2岁，P = 0.007）。静脉阿司匹林激发后，LTE 4的基础水平和尿LTE 4的增量并未显示野生型A纯合子和变异C等位基因携带者之间存在差异。有没有关系的多态性和LTC 4S活性的嗜酸性粒细胞，虽然LTC 4S活性显着高于AIA患者比患者ATA。结论：我们的研究结果揭示了缺乏功能的LTC 4S基因的多态性，而这种多态性可能有一定的影响，AIA的发展，可能与另一个致病的重要突变的连锁不平衡。
Background: The A to C transversion in the promoter region of the gene encoding leukotriene C-4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA).Objective: We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production.Methods: Genotyping of LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. We assessed the basal levels of urinary LTE4, the increment of urinary LTE4 on venous aspirin challenge, and LTC4S activity in peripheral blood eosinophils.Results: The frequency of the variant C allele was significantly higher in patients with AIA (frequency of allele [q] = 0.192) than in patients with ATA (q = 0.110, P = .042). Variant C-allelic carriers experienced asthma at a significantly younger age (31.8 +/- 2.9 years [mean +/- SEM]) than wild-type A homozygotes (41.3 +/- 2.2 years, P = .007). Basal levels of LTE4 and the increment of urinary LTE4 on venous aspirin challenge did not show a difference between wild-type A homozygotes and variant C-allelic carriers. There was no relationship between the polymorphism and the LTC4S activity in eosinophils, although LTC4S activities were significantly higher in patients with AIA than in patients with ATA.Conclusion: Our findings reveal the lack of functionality of the polymorphism in the LTC4S gene, whereas this polymorphism might have some effect on the development of AIA, probably in linkage disequilibrium with another causatively important mutation.