Sallakci Nilgun, Akcurin Gayaz, Köksoy Sadi, Kardelen Firat, Uguz Aysen, Coskun Mesut, Ertug Halil, Yegin Olcay
Central Research and Immunology Laboratories, Tip Fakultesi Kampus, Antalya 07070, Turkey.
J Autoimmun. 2005 Sep;25(2):150-4. doi: 10.1016/j.jaut.2005.05.005. Epub 2005 Jul 19.
Previous studies suggested that abnormal regulation of TNF-alpha production may have a role in the pathogenesis of rheumatic fever (RF). Polymorphism at the promoter region of TNF-alpha gene (-308 A) has recently been shown to be associated with rheumatic heart disease (RHD) in Mexican patients. Although this polymorphism has long been shown to affect TNF-alpha gene expression in cell lines, its role in production of the cytokine in RF patients has not been studied. We therefore investigated TNF-alpha G-308A single nucleotide polymorphism and its effect on TNF-alpha production in 71 Turkish RF patients and 89 ethnically matched healthy controls. The TNF-alpha-308A allele frequency was found to be significantly higher in RF patients (RHD+arthritis) than in healthy controls [p<0.0032 Odds ratio (OR)=3.4, 95% confidence interval (CI) (1.5-7.7)]. When RHD patients were analyzed as a separate group, significant difference persisted [p<0.0055, OR=3.3, 95% CI (1.5-7.6)]. More importantly, ELISPOT analysis demonstrated that existence of A allele was associated with higher TNF-alpha production compared with G allele. Our data suggest that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop RF disease.
先前的研究表明，肿瘤坏死因子-α（TNF-α）产生的异常调节可能在风湿热（RF）的发病机制中起作用。最近发现，TNF-α基因启动子区域的多态性（-308A）与墨西哥患者的风湿性心脏病（RHD）有关。尽管长期以来已证明这种多态性会影响细胞系中TNF-α基因的表达，但其在RF患者细胞因子产生中的作用尚未得到研究。因此，我们调查了71例土耳其RF患者和89例种族匹配的健康对照者中TNF-α G-308A单核苷酸多态性及其对TNF-α产生的影响。发现RF患者（RHD +关节炎）中TNF-α -308A等位基因频率明显高于健康对照者[p <0.0032，优势比（OR）= 3.4，95％置信区间（CI）（1.5-7.7）]。将RHD患者作为一个单独的组进行分析时，差异仍然显著[p <0.0055，OR = 3.3，95％CI（1.5-7.6）]。更重要的是，酶联免疫斑点分析（ELISPOT）表明，与G等位基因相比，A等位基因的存在与更高的TNF-α产生相关。我们的数据表明，携带高反应性TNF-α -308A等位基因可能是增加患RF疾病易感性的遗传因素。
