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白细胞介素-10基因-627等位基因变异与特应性支气管哮喘相关,而非白细胞介素-1β基因和受体拮抗剂基因多态性。

Interleukin-10 gene -627 allele variants, not interleukin-I beta gene and receptor antagonist gene polymorphisms, are associated with atopic bronchial asthma.

作者信息

Hang Liang-Wen, Hsia Te-Chun, Chen Wen-Chi, Chen Huey-Yi, Tsai Jeffrey J P, Tsai Fuu-Jen

机构信息

Department of Chest, China Medical College Hospital, Taichung, Taiwan.

出版信息

J Clin Lab Anal. 2003;17(5):168-73. doi: 10.1002/jcla.10088.

Abstract

Asthma is an airway hyperresponsive disease characterized by the expression of multiple inflammatory genes, including cytokines. Interleukin-I and interleukin-10 (IL-1 and IL-10) are cytokines that might play a role in the process of inflammation and are therefore considered to be involved in the pathogenesis of bronchial asthma. The aim of this study was to test whether the polymorphisms of the promoter region and exon 5 of the IL-1 gene, intron 2 of the IL-1Ra gene, and -627 nucleotide (C/A) of the IL-10 gene could be genetic markers for the susceptibility of bronchial asthma. A normal control group made up of 47 healthy volunteers and 117 patients with bronchial asthma were examined in this study. We analyzed the variable number of tandem repeats at intron 2 of the IL-1Ra gene for the polymorphisms by polymerase chain reaction (PCR). PCR-based restriction analysis of the IL-1 gene polymorphisms of the promoter region and exon 5 was carried out by the endonucleases Ava I and Taq I, respectively. The IL-10 gene -627 C/A polymorphisms were investigated by PCR-based restriction analysis. The distribution of CC homozygotes in the IL-10 gene was significantly lower in asthma patients than in controls (P=0.013, OR=3.599, 95% CI=1.240 approximately 10.441). The polymorphisms studied in the IL-1 genes did not reveal any significant association with bronchial asthma when compared with the control group (promoter region by chi-square test, P=0.627; exon 5 region by Fisher's exact test, P=0.403). Only two alleles of the IL-1Ra gene corresponding to one and two copies of an 86-base pair sequence repeat were identified by PCR in the control group. There were three alleles found in the asthmatic patient group. The results revealed no significant differences between normal individuals and asthma patients (P=0.454, Fisher's exact test). The IL-10 gene -627 "A" allele is an associated risk factor of developing atopic asthma.

摘要

哮喘是一种气道高反应性疾病,其特征是多种炎症基因的表达,包括细胞因子。白细胞介素 -I 和白细胞介素 -10(IL-1 和 IL-10)是可能在炎症过程中起作用的细胞因子,因此被认为与支气管哮喘的发病机制有关。本研究的目的是测试 IL-1 基因启动子区域和外显子 5、IL-1Ra 基因内含子 2 以及 IL-10 基因 -627 核苷酸(C/A)的多态性是否可能是支气管哮喘易感性的遗传标记。本研究对由 47 名健康志愿者组成的正常对照组和 117 例支气管哮喘患者进行了检查。我们通过聚合酶链反应(PCR)分析了 IL-1Ra 基因内含子 2 处串联重复序列的可变数目以检测多态性。分别通过核酸内切酶 Ava I 和 Taq I 对 IL-1 基因启动子区域和外显子 5 的多态性进行基于 PCR 的限制性分析。通过基于 PCR 的限制性分析研究 IL-10 基因 -627 C/A 多态性。哮喘患者中 IL-10 基因 CC 纯合子的分布显著低于对照组(P = 0.013,OR = 3.599,95% CI = 1.240 至 10.441)。与对照组相比,IL-1 基因研究的多态性未显示与支气管哮喘有任何显著关联(启动子区域通过卡方检验,P = 0.627;外显子 5 区域通过 Fisher 精确检验,P = 0.403)。在对照组中通过 PCR 仅鉴定出与 86 个碱基对序列重复的一份拷贝和两份拷贝相对应的 IL-1Ra 基因的两个等位基因。在哮喘患者组中发现了三个等位基因。结果显示正常个体和哮喘患者之间无显著差异(P = 0.454,Fisher 精确检验)。IL-10 基因 -627“A”等位基因是患特应性哮喘的相关危险因素。

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