系统性红斑狼疮患者血浆DNA p16基因启动子的甲基化状态  

Promoter Hypermethylation of p16 Gene in the Plasma of Patients with Systemic Lupus Erythematosus

作　　者：李遇梅[1] 李安生[1] 姚煦[1] 徐冠东 弓娟琴[1] 陈志强[1] 

机构地区：[1]中国医学科学院,中国协和医科大学皮肤病研究所,南京210042 [2]中国医学科学院,中国协和医科大学肿瘤研究所病因室

出　　处：《中华皮肤科杂志》2005年第7期419-422,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金资助项目(30170863)江苏省自然科学基金资助项目(BK2001195)

摘　　要：目的探讨系统性红斑狼疮(SLF)患者中p16基因的甲基化状态及其在发病机制中的作用。方法检测45例SLE患者及20例健康对照者血浆DNA甲基化状态。应用甲基化特异PcR(MSP) 方法检测p16基因启动子区甲基化状态,并分析与临床表现及常规实验室检查结果之间的关联。结果在SLE患者血浆DNA中p16基因呈现高甲基化状态,占64.44%(29/45),而健康对照组中只有1例检测到p16基因高甲基化(1/20,5%),两组间差异有统计学意义(x2=19.69,P<0.01)。活动期SLE组p16基因呈高甲基化状态者所占比率83.33%(20/24),比非活动期SLE组42.85%,(9/21)高,差异也有统计学意义(x2=8.01;P<0.01)。但初发SLE组p16基因呈高甲基化状态者所占比例(71.43%,15/21)与复发SLE 组(58.33%,14/24)相比差异无统计学意义(P=0.37)。具有下列临床表现的SLE患者其血浆p16基因高甲基化状态者所占比率相对较高:关节炎(57.5%,15/26),白细胞减少(42.3%,11/26),血沉增快(56%,14/ 25)。结论活动期SLE患者血浆DNA p16基因启动子区呈现明显高甲基化状态,并与关节炎、白细胞减少及血沉增快等临床表现相关;提示p16基因启动子区高甲基化可能在SLE的发病机制中起作用。Objective To detect p16 gene DNA methylation in the plasma of patients with systemic lupus erythematosus (SLE) and its significance in the disease activity and clinical manifestations. Methods Forty-five cases of SLE and 20 healthy controls were enrolled. Promoter methylation in p16 gene was measured by methylation specific PCR (MSP) in patients' plasma, and the correlation between the methylation status and clinical manifestations and routine laboratory findings were analyzed. Results Hypermethylation of p16 gene DNA was observed in the plasma of SLE. It was found that the rate of DNA hypermethylation was significantly higher in active SLE patients (20/24, 83.33%) than that in inactive patients (9/21, 42.85%) (x2 = 8.008 b; P< 0.01 ), but not between the first onset SLE (71.43%, 15/21) and recurrent SLE (58.33%, 14/24) (P- 0.371 ). DNA hyermethylation was detected in only one healthy control. The difference of the rate of DNA hyermethylation was significant between SLE patients (29/45, 64.44%) and healthy individuals(1/20, 5%) (x2 = 19.687, P< 0.001 ). The SLE patients with hypermethylation of p16 gene seemed more susceptible to have arthritis(57.5%, 15/26), leukopenia (42.3%, 11/26) and elevated erythrocyte sedimentation rate (ESR)(56%, 14/25) as compared with those without hypermethylation. A statistically significant correlation was found between the p16 gene hypermethylation and the presence of arthritis (P= 0.019), leukopenia(P = 0.016), and elevated ESR (P = 0.026). Conclusions It is demonstrated that promoter methylation of p16 gene is significantly aberrant in SLE patients. From our study, p16 gene may be involved in the pathogenesis of SLE. It is suggested that there is a certain degree of relationship between DNA hypermethylation and the disease activity and clinical manifestations.

关 键 词：系统性红斑狼疮 血浆DNA P16基因启动子 甲基化状态 SLE MSP DNA甲基化 

分 类 号：R593.241[医药卫生—内科学]