Ates O, Musellim B, Ongen G, Topal-Sarikaya A
Department of Molecular Biology and Genetics, Science Faculty, Istanbul University, 34118 Vezneciler, Istanbul, Turkey.
J Clin Immunol. 2008 May;28(3):232-6. doi: 10.1007/s10875-007-9155-2.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease in humans killing nearly three million people and eight million cases annually. The cytokines TNF-alpha and IL-10 have been implicated in the pathogenesis of TB. Certain single nucleotide polymorphisms within the promoter region of the IL10 and TNF genes have been associated with altered levels of circulating IL10 and TNF-alpha. We analyzed TNF-alpha (-308 G/A, -238 G/A, -376 G/A) and IL10 (-1,082 G/A, -819 C/T, -592 C/A) polymorphisms in 128 patients with TB and 80 healthy subjects using by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). A significant association was found between TB and -1,082 G allele (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41). Significant difference was observed in IL10 GCC and ACC haplotypes distribution between TB and control subjects (Pc: 0.000, O.R 2.22, 95% CI 1.45-3.41; Pc: 0.004, O.R 0.53, 95% CI 0.35-0.81). No statistically significant association was found between IL-10 -819 C/T, TNF-alpha 308 G/A, -238 G/A, -376 G/A polymorphisms, functional TNFalpha/IL-10 genotypes and TB. Our findings suggest that IL-10 1082 G/A alleles or haplotypes containing these alleles may influence the Th1/Th2 balance and hence may play a role in TB susceptibility and increase risk of developing disease. This polymorphism may be one of the many genetic factors affecting disease outcome.
由结核分枝杆菌引起的结核病是一种人类传染病,每年导致近300万人死亡,800万例发病。细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)与结核病的发病机制有关。IL10和TNF基因启动子区域内的某些单核苷酸多态性与循环中IL10和TNF-α水平的改变有关。我们采用扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)分析了128例结核病患者和80名健康对照者的TNF-α(-308 G/A、-238 G/A、-376 G/A)和IL10(-1082 G/A、-819 C/T、-592 C/A)多态性。发现结核病与-1082 G等位基因之间存在显著关联(Pc:0.000,比值比2.22,95%可信区间1.45-3.41)。在结核病患者和对照者之间观察到IL10 GCC和ACC单倍型分布存在显著差异(Pc:0.000,比值比2.22,95%可信区间1.45-3.41;Pc:0.004,比值比0.53,95%可信区间0.35-0.81)。未发现IL-10 -819 C/T、TNF-α 308 G/A、-238 G/A、-376 G/A多态性、功能性TNFα/IL-10基因型与结核病之间存在统计学显著关联。我们的研究结果表明,IL-10 1082 G/A等位基因或包含这些等位基因的单倍型可能影响Th1/Th2平衡,因此可能在结核病易感性中起作用,并增加发病风险。这种多态性可能是影响疾病结局的众多遗传因素之一。