白细胞介素-6启动子DNA甲基化在系统性红斑狼疮发病中的作用

Effect of interleukin-6 promoter DNA methylation on the pathogenesis of systemic lupuserythematosus

目的分析系统性红斑狼疮（SLE）患者外周血中白细胞介素（IL）-6启动子DNA甲基化状态及其在系统性红斑狼疮发病机制中的作用。方法选择41例在广州市第一人民医院风湿免疫内科住院的活动期SLE患者和20例健康对照者为研究对象，用甲基化特异性PCR（MSP）方法检查全血及外周血单个核细胞（PBMC）中IL-6启动子DNA甲基化状态，用qRT-PCR方法检测IL-6mRNA的表达水平，分析IL-6启动子DNA甲基化状态与SLE患者实验室参数和脏器损害的关系。结果（1）IL-6mRNA在SLE患者外周血及PBMC中的表达均增加，SLE患者外周血中IL-6的表达是对照组外周血IL-6表达的（1.63±0.69）倍，SLE患者PBMC中IL-6的表达是对照组PBMC中IL-6表达的（1.66±0.71）倍，差异均有统计学意义（均P〈0.001）；（2）32例（78%）SLE患者外周血中IL-6基因发生低甲基化，较正常对照样本中6例（30%）DNA低甲基化发生率高（P〈0.05），外周血中IL-6基因甲基化状态与该患者PBMC中甲基化状态的差异无统计学意义；（3）SLE患者外周血IL-6基因DNA甲基化状态与补体C3、C4的降低相关（P〈0.05）；（4）SLE患者外周血IL-6基因DNA低甲基化状态与肾脏损害相关（P〈0.05）。结论SLE患者外周血中IL-6启动子DNA呈低甲基化状态，且与补体C3、C4的降低及肾脏损害相关，提示IL-6启动子DNA低甲基化可能参与SLE的发病。

ObjectiveTo analyze peripheral blood interleukin-6 （IL-6） promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus （SLE）.MethodsBlood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction （MSP）. The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed.ResultsThe levels of IL-6 mRNA were significantly higher in peripheral blood of SLE.DNA methylation levels of IL-6 promoter were reduced in SLE patients as compared with healthy controls.The methylation status and expression of IL-6 in peripheral blood reflected the levels in peripheral blood mononuclear cells （PBMCs）. Significantly positive correlation was found between IL-6 hypomethylation and renal disorder, as well as hypocomplementemia in patients with SLE.ConclusionHypomethylation of interleukin-6 promoter in peripheral blood might be involved in the etiology of SLE.