目的探讨DNA甲基转移酶1(DNMT1)、甲基转移酶3a(DNMT3a)、甲基转移酶3b(DNMT3b)与CD11a的相互关系,以及与中国广西人群中原发性抗中性粒细胞胞质抗体(ANCA)相关性小血管炎(AAV)发病的相关关系。方法采用荧光定量一聚合酶链反应(qRT-PCR)技术检测3种甲基转移酶以及CD11a的mRNA在33例广西活动期AAV患者和45名健康对照组外周血单个核细胞中的表达,采用t检验及Spearman、Pearson进行相关分析。结果①AAV患者组的DNMT1的mRNA表达水平0.5±0.3明显低于健康对照组0.8±0.3,差异有统计学意义(t=4.446,P〈0.01);②AAV患者组的DNMT3a、DNMT3b的mRNA表达水平与健康对照组之间的差异无统计学意义(P〉0.05);③AAV患者组的CD11a的mRNA表达水平0.63±0.46高于健康对照组0.04±0.22(t=2.402,P〈0.05);④AAV患者中DNMT1的表达水平与患者BAVS评分呈负相关(r=-0.414,P〈0.05);⑤AAV患者中CD11a的表达水平与BAVS评分呈正相关(r=0.435,P〈0.05);⑥AAV患者中DNMT1与CD11a的表达水平呈负相关(r=-0.15,P〈0.05)。⑦AAV患者中BAVS评分与肾脏病理活动指数(AI)呈正相关(r=0.786,P〈0.05)。结论中国广西人群中,AAV患者外周血单个核细胞中DNMT1基因表达的降低可能是造成DNA低甲基化的重要原因,可能诱导CD11a等相关致病基因过度表达从而引起AAV的发病。
Objective To investigate the relationship of DNA methyltransferasei 1 (DNMT1), methyl- transferase 3a (DNMT3a), Methyhransferase 3b(DNMT3b) and CD1 la in ANCA-assodated vasculitis (AAV) in Chinese Guangxi population. Methods The mRNA level of three kinds of DNMT and CDlla in the peripheral blood mononuclear cells (PBMC) from 33 cases with active AAV and 45 healthy controls were examined by fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR), the difference in gene expression was compared between the AAV groups and healthy controls. T-test was used for statistical analysis. Correlation analysis was used for gene expression analysis between the AAV groups and its clinical BVAS score and the correlation between renal pathological activity index (AI). Results ① Statistical significant difference was found in the mRNA expression of DNMT1 between the AAV group 0.5 ±0.3 and healthy controls 0.8±0.3 (t=4.446, P〈0.01). The expression of DNMT1 in PBMC was decreased significantly than that in healthy controls. ② No statistical significant difference was found in the mRNA expression of DNMT3a and DNMT3b between the AAV group and healthy controls (P〉0.05). ③Statistical significant differ- ence was found in the mRNA expression of CDlla between the AAV group 0.63±0.46 and healthy controls 0.44±0.22 (t=2.402, P〈0.05). The mRNA expression of CDlla in PBMC was higher than healthy controls.④ The mRNA expression levels of DNMTt in PBMC of AAV patients and BVAS score showed a negative correlation (r=-0.414, P〈0.05). ⑤The mRNA expression levels of CDlla in PBMC of AAV patients and BVAS score was positively correlated (r=0.435, P〈0.05). ⑥ The mRNA expression levels of DNMT1 and CDlla were negatively correlated (r=-0.15, P〈0.05). ⑦Renal pathological activity index (AI) and BVAS score of the AAV patients was positively correlated (r=0.786, P〈0.05). Conclusion The decreased expression of DNMT1 may result in the declin