Association of asthma severity and bronchial hyperresponsiveness with a polymorphism in the cytotoxic T-lymphocyte antigen-4 gene
Association of asthma severity and bronchial hyperresponsiveness with a polymorphism in the cytotoxic T-lymphocyte antigen-4 gene
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DOI：
10.1378/chest.122.1.171
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发表时间：
2002-07-01
期刊：
影响因子：
9.6
通讯作者：
In, KH
中科院分区：
文献类型：
--
作者：
Lee, SY;Lee, YH;In, KH
目的：细胞毒性T淋巴细胞抗原(CTLA)-4是CD28的同源物，仅在活化的T细胞上表达。它与辅助分子B7结合，介导t细胞依赖性免疫反应。通过CTLA-4信号传导可能下调I型t辅助细胞的增殖；此外，声学研究表明CTLA-4也可能为2型t辅助细胞激活传递阳性信号。这种微妙的免疫调节平衡的破坏可能导致自身免疫性疾病或特应性疾病。为了评估CTLA-4多态性在支气管哮喘中的可能作用，我们在支气管哮喘患者和一组健康对照中研究了多态性（外显子1 +49 A/G，启动子-318 C/T）与特应性、哮喘严重程度和支气管高反应性之间的关系。患者：88例哮喘患者和88例健康对照。测量和结果：哮喘严重程度评估、甲胆碱激发、过敏皮肤点刺试验和血清总IgE测定。采用聚合酶链反应和限制性片段长度多态性测定所有受试者CTLA-4启动子（-318 C/T）和外显子1 （+49 A/G）的基因型。CTLA-4启动子（- 3 18 C/T）多态性与哮喘严重程度相关，但与哮喘、特应性或支气管高反应性无关。严重哮喘与T等位基因之间存在显著相关性（p = 0.037）。CTLA-4外显子1 （+49 A/G）多态性与支气管高反应性有关，但与哮喘、特应性或哮喘严重程度无关。GG基因型哮喘患者气道高反应性高于AG、AA基因型哮喘患者（p = 0.019）。结论：CTLA-4启动子（-318 C/T） T等位基因可能是临床上有用的重度哮喘标志物。CTLA-4外显子1 （+49 A/G）多态性可能在哮喘气道中具有疾病改善作用。
Objectives: Cytotoxic T-lymphocyte antigen (CTLA)-4 is a homolog of CD28, which is expressed only on activated T cells. It binds to accessory molecule B7 and mediates T-cell-dependent immune response. Signaling through CTLA-4 may down-regulate type I T-helper cell proliferation; moreover, sonic studies suggest that CTLA-4 might also deliver a positive signal to type 2 T-helper cell activation. Disruption of this delicate balance of immune regulation may lead to autoimmune diseases or atopic diseases. To evaluate the possible role of CTLA-4 polymorphisms in bronchial asthma, we investigated the association between polymorphisms (exon 1 +49 A/G, promoter -318 C/T) and atopy, asthma severity, and bronchial hyperresponsiveness in bronchial asthma patients and a group of healthy control subjects.Patients: Eighty-eight asthmatic patients and 88 healthy control subjects were studied.Measurements and results: Asthma severity assessment, methacholine challenge, allergy skin-prick test, and serum total IgE measurements were performed. The genotypes of the CTLA-4 promoter (-318 C/T) and exon 1 (+49 A/G) in all subjects were determined using the polymerase chain reaction and restriction fragment length polymorphism. The CTLA-4 promoter (- 3 18 C/T) polymorphism was shown to be associated with asthma severity, but not with asthma, atopy, or bronchial hyperresponsiveness. A significant association was found between severe asthma and the T allele (p = 0.037). The CTLA-4 exon 1 (+49 A/G) polymorphism was shown to be associated with bronchial hyperresponsiveness, but not with asthma, atopy, or asthma severity. Asthmatic patients of the GG genotype had more hyperresponsive airways than those with the AG or AA genotype (p = 0.019).Conclusions: The CTLA-4 promoter (-318 C/T) T allele may serve as a clinically useful marker of severe asthma. The CTLA-4 exon 1 (+49 A/G) polymorphism may have a disease-modifying effect in asthmatic airways.