Analysis of genetic polymorphisms which effects on tuberculosis

影响结核病的基因多态性分析

基本信息

批准号：
12670428
负责人：
NAKASHIMA Hitoshi
金额：
$ 2.3万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

CD4+ helper T (Th) cells can be classified into two different subsets based on their patterns of cytokine production. Th1 cells produce mainly interferon-γ (IFN-γ) and interleukin-2 (IL-2) and promote cell-mediated immunity, whereas Th2 cells secreting IL-4, IL-5, IL-6 and IL-10, are associated with humoral immune responses and induce antibody production. It has been demonstrated that an imbalance between Th1 and Th2 cytokine production is very much concerned with the induction and development of several autoimmune diseases, a correction of this Th1/Th2 balance has in fact led to the prophylaxis and therapy of such diseases in various models of autoimmunity.Tuberculosis is the leading single infectious cause of death worldwide, claiming about 3 million lives annually, and approximately one-third of the world's population is infected with Mycobacterium tuberculosis. Twin, adoption and ethnic studies have indicated that host genetic differences in immune response may affect susceptibilit … More y to mycobacterial infection. Earlier genetic association studies have shown that severe pulmonary tuberculosis was associated with both HLA-DR2 and haptoglobin 2-2. Recently, other studies have revealed polymorphisms in the IL-1 locus, human NRAMP1 gene, vitamin D receptor gene, and HLA-DQ allele also contribute to susceptibility to tuberculosis.To date, genetic deficiencies in five genes involved in the type 1 cytokine cascade (IL-12p40, IFN-gR1, IFN-gR2, IL-12Rb1 and STAT1) have been shown to render hosts susceptible to poorly pathogenic mycobacteria, such as bacillus Calmette Guerin (BCG) and environmental nontuberculous mycobacteria (NTM). These reports highlighted the critical role of IFN-γ-mediated immunity in protection against intracellular pathogens. The absence of such key cytokine or cytokine receptors results in a dramatic clinical phenotype, usually lethal in early childhood, while more subtle polymorphisms which result in only partial impairment of the type-1 cytokine cascade may play a role in susceptibility to tuberculosis among the general population. Here we have searched for polymorphisms in both the β1 and β2 subunits of the IL-12 receptor. We then determined whether IL-12 receptor polymorphisms are associated with susceptibility to tuberculosis by performing a case-control study comparing the frequency of IL12RB1 genotypes in Japanese subjects with tuberculosis and healthy controls. We also confirmed the effect of human IL-12R polymorphisms on IL-12-induced biologic activities, using several functional assays. Less

CD4+辅助剂t（Th）细胞分类了两个不同的subsent，以其细胞因子的产生模式）和白介素-2（IL-2），并促进细胞介导的IMUNITY，而Th2细胞分泌IL-4，IL-5 ，IL-6和IL-10与体液IL-10有关。实际上，在各种自身免疫性模型中导致了这种容易的预防和治疗。Tubercullcullosis是全球死亡世界的主要单一感染原因，每年夺走了大约300万人的生命，大约三分之一的人是结核病的感染世界的三分之一。表明宿主的遗传差异可能会影响敏感性……更多的Yn YCOBACTERIAL感染表明，严重的肺结核与HLA-DR2和HLA HLA 2-2均与HLA-DR2相关。等位基因还有助于迄今为止的结核病，涉及五个基因的遗传缺陷（IL-12PP40，IFN-GR1，IFN-GR1，IFN-GR2，IL-12RB1和STAT1）使宿主易于易于致病的芽孢杆菌Calmette Guerin（BCG）和环境非结核分枝杆菌（NTM），反对细胞内病原体。 -1一般人群中的结核病。活动，使用严重性功能测定。