Kawagishi Yukio, Mita Haruhisa, Taniguchi Masami, Maruyama Muneharu, Oosaki Rokuo, Higashi Noritaka, Kashii Tatsuhiko, Kobayashi Masashi, Akiyama Kazuo
First Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
J Allergy Clin Immunol. 2002 Jun;109(6):936-42. doi: 10.1067/mai.2002.124466.
The A to C transversion in the promoter region of the gene encoding leukotriene C4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA).
We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production.
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.
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.
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.
白三烯C4合成酶(LTC4S)编码基因启动子区域的A到C颠换被认为与阿司匹林诱发哮喘(AIA)的发生有关。
我们调查了该多态性在日本人群中的频率及其与临床特征和半胱氨酰白三烯产生的关联。
对60例AIA患者、100例阿司匹林耐受型哮喘(ATA)患者和110名对照者进行LTC4S基因启动子的基因分型。我们评估了尿LTE4的基础水平、静脉注射阿司匹林激发试验后尿LTE4的增加量以及外周血嗜酸性粒细胞中的LTC4S活性。
AIA患者中变异C等位基因的频率(等位基因频率[q]=0.192)显著高于ATA患者(q=0.110,P=0.042)。变异C等位基因携带者患哮喘的年龄(31.8±2.9岁[均值±标准误])明显低于野生型A纯合子(41.3±2.2岁,P=0.007)。野生型A纯合子和变异C等位基因携带者之间,LTE4的基础水平以及静脉注射阿司匹林激发试验后尿LTE4的增加量没有差异。尽管AIA患者的LTC4S活性显著高于ATA患者,但该多态性与嗜酸性粒细胞中的LTC4S活性之间没有关系。
我们的研究结果揭示了LTC4S基因多态性缺乏功能性,而这种多态性可能对AIA的发生有一定影响,可能与另一个具有致病重要性的突变处于连锁不平衡状态。