CD86功能多态性与哮喘及相关的变态反应性疾病相关
2007/08/01
一些研究报道了过敏性疾病的发生与基因存在确实的相关性，而且提出了遗传过敏体质的易感基因位点。其一为3q21，据报道与多种遗传过敏体质的表现型相关。CD86基因在此位点，编码联合刺激因子B7.2蛋白。联合刺激系统由多种蛋白质受体，细胞因子及相关因子组成，功能为激活T细胞，调节抗原刺激引发的免疫反应。作者测定了来源10个家庭的遗传过敏体质患者的CD86基因序列，这些患者均表现出与3q21相关的证据。鉴定的多态型利用家系为基础的联合研究进行分析，选取的人群是来自丹麦的两个独立的样品人群，均由135和100个遗传过敏体质患者三代组成。联合刺激因子对细胞因子生成影响的功能分析采用自体来源的表达CD86突变体的细胞体系。
结果显示，两个分别编码突变氨基酸的多态型，Ile179Val 和Ala304Thr, 被鉴定。在两组样品中，Ile179Val多态型和过敏的表现型明确相关（例如，哮喘，两组的合并结果是p=0.004）；已发现保护性的Val179等位基因较危险的Ile179等位基因诱导更高水平的Th1细胞因子(IL-2, TNF-alpha, INF-gamma)，和Th2细胞因子 (IL-4, IL-5)，表明该多态型导致的功能缺陷。
作者得出结论：CD86基因，特别是Ile179Val多态型，可能是一个新发现的哮喘和相关过敏性疾病的致病因子。
作者得出结论：CD86基因，特别是Ile179Val多态型，可能是一个新发现的哮喘和相关过敏性疾病的致病因子。
（韩福军 广州医学院第一附属医院 广州呼吸疾病研究所 510120 摘译）
(J Med Genet. 2007 May 18)
Corydon TJ, Haagerup A, Jensen TG, Binderup HG, Petersen MS, Kaltoft K, Vestbo J, Kruse TA, B?rglum AD.
A functional CD86 polymorphism associated with asthma and related allergic disorders.
J Med Genet. 2007 May 18
BACKGROUND: Several studies have documented a substantial genetic component in the aetiology of allergic diseases, and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21 where linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulate the immune response upon allergen challenge.
METHODS: We sequenced the CD86 gene in atopic patients from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analyzed in a subsequent family based association study of two independent Danish samples comprising 135 and 100 atopic case-parents trio families, respectively. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants.
RESULTS: Two polymorphisms were identified encoding the amino-acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (e.g.: asthma, p=0.004 in the two samples combined). The under-transmitted (protective) Val179 allele was found to induce higher production of both Th1 cytokines (IL-2, TNF-alpha, INF-gamma) and Th2 cytokines (IL-4, IL-5) than the over-transmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism.
CONCLUSION: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.
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IL4受体α突变与哮喘发作及肥大细胞数量IgE表达相关
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