Genetic influence of PTPN22 R620W polymorphism in tuberculosis
Genetic influence of PTPN22 R620W polymorphism in tuberculosis
复制标题
DOI：
10.1016/j.humimm.2005.11.008
复制
发表时间：
2005-12-01
期刊：
影响因子：
2.7
通讯作者：
Martin, Javier
中科院分区：
文献类型：
--
作者：
Gomez, Luis M.;Anaya, Juan-Manuel;Martin, Javier
PTPN22基因编码一种细胞内淋巴特异性磷酸酶(LYP)，它对T细胞的激活具有负面调节作用。由于LYP是参与炎症反应的重要分子，并且在参与抗结核分枝杆菌免疫反应的细胞中其水平升高，我们推测功能性PTPN22 C1858T多态性可能是结核病发生的一个遗传因素。因此，我们进行了一项相关性研究，其中113名肺结核患者和161名匹配的健康对照通过结核菌素皮肤试验(TST)进行了分层检查。两组T等位基因频率比较(P=0.04，优势比=0.3；95%可信区间=0.08~1.04)与对照组比较(P=0.01，优势比=0.2；95%可信区间=0.05~0.79)，差异有统计学意义。在患者和对照样本之间没有检测到分层。这些结果表明，一旦免疫系统识别出结核分枝杆菌(即TST+个体)，T等位基因可能是防止结核病发展的因素，而C等位基因可能是发展为显性结核病的危险因素。研究结果还表明，PTPN22基因多态性与自身免疫之间存在着相反的关联关系。
The PTPN22 gene codes for an intracellular lymphoid-specific phosphatase (Lyp) that has a negative regulatory effect on T-cell activation. Because Lyp is an important molecule involved in the inflammatory response, and its levels are increased in cells that participate in the immune response against Mycobacterium tuberculosis, we hypothesized that the functional PTPN22 C1858T polymorphism could be a genetic factor predisposing to the development of tuberculosis (TB). Accordingly, we undertook an association study in which 113 patients with pulmonary TB and 161 matched healthy controls stratified by the tuberculin skin test (TST) were examined. Significant skewing was observed when T allele frequencies of patients with TB and all controls were compared (P = 0.04, odds ratio = 0.3; 95% confidence interval = 0.08-1.04) and frequencies of patients with TB and TST+ healthy controls were compared (P = 0.01, odds ratio = 0.2; 95% confidence interval = 0.05-0.79). No stratification was detected between patients and control samples. These results suggest that the T allele may be a factor protecting against development of TB once the immune system recognizes M. tuberculosis (i.e., TST+ individuals), whereas the C allele may be a risk factor for development of overt TB. The results also indicate that an association opposite that between the PTPN22 polymorphism and TB exists between TB and autoimmunity.