甘露糖结合凝集素基因多态性与重型狼疮肾炎进展的关系

Association of mannan- binding lectin gene polymorphisms with progression of severe lupus nephritis

目的探讨甘露糖结合凝集素（MBL）基因多态性与重型狼疮肾炎MBL血清水平、疾病发生、发展及预后的关系。方法选取2003年1月到2013年10月重型狼疮肾炎患者共107例为研究对象。收集基础和随访期间患者临床和相关生化指标资料。用毛细管电泳直接测序法检测MBL基因启动子区域和第一外显子多态性。用ELISA法检测MBL血清水平。Kaplan-Meier生存分析法分析rsll003125基因多态性与肾功能和肾脏预后的关系。COX回归模型分析影响肾脏预后的危险因素。结果rsll003125、rs7096206、rs7095891和rs1800450位点存在多态性。rsll003125位点GG基因型MBL血清水平〉GC基因型〉CC基因型（P〈0．01），rs7096206位点GG基因型MBL血清水平〉GC＋CC基因型（P〈0．01），rsl800450位点GG基因型MBL血清水平〉GA基因型（P〈0．01）。rsll003125位点GC＋CC基因型组起始收缩压、舒张压、平均动脉压、血肌酐、尿素氮及24h尿蛋白量显著高于GG基因型组（P〈0．05），肾小球滤过率、肾脏平均生存时间低于GG基因型组（P〈0．05）。重型狼疮肾炎进展组rsll003125位点GC＋CC基因型频率高于非进展组（91．9％比75．7％，P=0．041），进展组rs7095891位点cT＋rlTI、基因型频率高于非进展组（32．4％比14．3％，P=0．027）。结论重型狼疮。肾炎患者MBLrsll003125、rs7096206和rsl800450位点基因多态性影响MBL血清水平，rsl1003125位点基因多态性与重型狼疮肾炎起病严重程度、进展及肾脏预后相关。

Objective To investigate the association of single nueleotide polymorphisms （SNPs） of the mannan binding leetin （MBL） gene with serum levels, development, progression and prognosis of severe lupus nephritis （LN）. Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October 2013. Integrated capillary eleetrophoresis was used to detect MBL gene polymorphism in peripheral blood DNA. ELISA was used to detect serum MBL concentration. Kaplan- Meier survival analysis was used to analyse the relationship of renal function, kidney prognosis with the gene polymorphism of rs11003125. Cox regression model analysis was used to identify possible risk factors of kidney prognosis. Results SNPs in rs11003125, rs7096206, rs7095891 and rs1800450 were found. The serum MBL concentration of patients with GGgenotype in rs11003125 was higher than that with GC genotype, and both were higher than that with CC genotype （P〈 0.01）. Patients with SNP of rs11003125 had higher systolic blood pressure, diastolic blood pressure, mean arterial pressure, serum creatinine, urea nitrogen, 24 hours urinary protein, and lower glomerular filtration rate, shorter mean renal survival time （P 〈 0.05）. Progressive severe LN patients had higher GC ＋ CC （91.9% vs 75.7%, P = 0.041）, CT＋TF （32.4% vs 14.3%, P = 0.027） genotype frequencies at promoter rs11003125 and rs7095891, respectively, compared with that of non progressive severe LN patients. Conclusions rs11003125, rs7096206 and rs1800450 polymorphisms of MBL gene are associated with lower serum MBL levels in severe LN patients. rs11003125 promoter polymorphisms of MBL gene may contribute to the onset severity, progression and prognosis of severe lupus nephritis.