DNA甲基转移酶与CD11a基因在SLE患者中的表达

Expression of DNA methyltransferases and CD11a genes in systemic lupus erythematosus patients

目的探讨DNA甲基转移酶(DNMT)的表达异常在SLE发病中的作用。方法以半定量RT-PCR方法检测了SLE缓解期、活动期及正常人外周血单核细胞(PBMC)中DNMT及CD11a基因表达水平,并进行相关性分析。结果SLE缓解期患者PBMC中DNMT1的表达水平显著低于正常人对照组(t=5.90,P<0.0001);活动期的表达水平也显著低于对照组(t=2.26,P=0.0001);缓解期与活动期比较差异无统计学意义(t=1.75,P=0.089)。SLE缓解期、活动期及对照组PBMC中DNMT3A的表达水平差异无统计学意义,DNMT3B的表达水平极低。SLE缓解期PBMC中CD11a表达水平明显高于对照组(t=5.35,P<0.0001);活动期的表达水平显著高于缓解期(t=2.99,P=0.006)和正常人对照组(t=6.57,P<0.0001)。DNMT1的降低与SLE疾病活动指数(SLEDAI)间无显著相关性(r=-0.34,P>0.05),CD11a的升高与SLEDAI间呈显著正相关(r=0.48,P<0.05),DNMT1与CD11a间无显著相关性(r=-0.18,P>0.05)。结论DNMT1表达水平降低在SLE的发病中可能起作用。但不是决定DNA甲基化状态的惟一因素。

Objective To investigate the role of abnormal expression of DNA methyltmnsferases （DNMT1, DNMT3A, DNMT3B） and CD11a genes in the pathogenesis of systemic lupus erythematosus （ SLE ）. Methods Semiquantitative reverse transcriptase-polymerase chain reaction was applied to detect the mRNA expression levels of DNMTs and CDI la in PBMCs of relieved （ n = 17 ）, active （ n = 17 ） SLE patients and healthy controls （ n = 17 ）. The correlations were further analyzed between these parameters. Results The expression of DNMTI was significantly lower in PBMCs of both relieved and active SLE patients than that of health controls （ t = 5.90, P 〈 0.0001; t = 2.26, P = 0.0001 respectively ）. No significant difference was observed in DNMTI expression between relieved and active SLE patients （ t = 1.75, P = 0.089 ）, or in the expression of DNMT3A in PBMCs between relieved, active SLE patients and healthy conlrol. The expression of DNMT3B in PBMCs was extremely low. The expression of CD11a was significantly higher in relieved SLE patients than in the healthy controls （ t = 5.35, P 〈 0.0001 ）, in active SLE patients than in relieved SLE patients （ t = 2.99, P = 0.006 ） and healthy controls （ t = 6.57, P 〈 0.0001 ）. No significant correlation was observed between the decrease of DNMTI and SLE disease activity index （ SLEDAI ） （ r = -0.34, P 〉 0.05 ）, or between the expression level of DNMTI and CDI la （ r = -0.18, P 〉 0.05 ）. The increase of CD11a positively correlated with SLEDAI （ r = 0.48, P 〈 0.05 ）. Conclusion The decreased expression of DNMTI may play an important role in the pathogenesis of SLE, but not the only factor contributing for DNA methylation status.