Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV

ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

摘要 研究背景：铁调素（Hepcidin）与慢性肾衰竭贫血的发病机制相关，而慢性肾衰竭贫血与丙型肝炎病毒（HCV）感染均被认为属于慢性炎症状态。白细胞介素6（IL-6）可刺激肝脏释放铁调素，抑制肠道铁摄取，并从体内铁储存池中释放铁元素。
研究方法：为探讨IL-6基因多态性与贫血标志物的关联，本研究纳入80例血液透析（HD）患者，其中HCV阴性血液透析患者40例、HCV阳性血液透析患者40例。所有受试者均接受常规生化检测与全血细胞计数，同时检测血清铁调素、铁代谢指标[血清铁与血清铁蛋白]及丙型肝炎病毒标志物。采用多重聚合酶链反应（MS-PCR）检测IL-6基因-174G/C多态性，采用聚合酶链反应-序列特异性引物法（PCR-SSP）检测IL-6基因-597G/A与-572G/C多态性。
研究结果：与HCV阴性血液透析患者相比，HCV阳性患者的血清铁调素水平无显著性升高。HCV阴性与阳性血液透析患者的IL-6 -174G/C及-597G/A多态性频率存在统计学显著差异（分别为P≤0.01与P≤0.001）；而IL-6 -572G/C多态性频率在两组间无统计学差异。
研究结论：本研究提示，IL-6 -174G/C与-597G/A多态性可能在血液透析患者的HCV易感性中发挥作用。未来需开展更大样本量的前瞻性研究以验证本研究结论。