IgA肾病患者外周血单个核细胞Klotho基因甲基化水平与肾功能的相关性  

Elevated Klotho promoter methylation of peripheral blood mononuclear cells is associated with deterioration of renal function in IgA nephropathy patients

作　　者：陈静[1] 张函[1] 章晓燕[1] 丁小强[1] 

机构地区：[1]复旦大学附属中山医院肾内科,上海市肾病与透析研究所,上海市肾脏疾病与血液净化重点实验室,上海200032

出　　处：《上海医学》2016年第5期260-264,共5页Shanghai Medical Journal

基　　金：科技部国家科技支撑项目(2011BAI10B03);上海市科学技术委员会自然科学基金(14ZR1406400)资助

摘　　要：目的分析IgA肾病患者外周血单个核细胞(PBMC)Klotho基因甲基化水平与肾功能的相关性。方法选择2012年8月—2013年2月在复旦大学附属中山医院肾内科住院治疗,并经活组织病理学检查证实为原发性IgA肾病,且临床和病理资料完整的70例患者,采用焦磷酸测序法检测PBMC Klotho基因甲基化率,分析PBMC Klotho基因甲基化率与临床指标的相关性。结果70例IgA肾病患者中,男39例,女31例;平均年龄为(37.9±11.8)岁;估算肾小球滤过率(eGFR)为49.2(34.1,65.4)mL/(min·1.73 m^2);PBMC Klotho基因甲基化率为4.1%(2.7%,6.0%)。eGFR>60 mL/(min·1.73 m^2)、eGFR为30~60mL/(min·1.73m^2)和eGFR<30 mL/(min·1.73 m^2)患者的PBMC Klotho甲基化率分别为2.7%(2.0%,2.8%)、4.5%(3.5%,6.1%)和6.9%(5.5%,9.1%),前者的PBMC Klotho甲基化率显著低于后两者(P值均<0.01),eGFR为30~60 mL/(min·1.73 m^2)者的PBMC Klotho甲基化率又显著低于eGFR<30mL/(min·1.73m^2)者(P<0.01)。多因素线性回归分析结果显示,eGFR降低是IgA肾病患者PBMC Klotho甲基化率升高的独立危险因素(β=-0.551,P<0.001)。结论 IgA肾病患者PBMC Klotho基因的甲基化水平与肾功能相关,随着肾功能减退,IgA肾病患者PBMC Klotho基因甲基化水平升高。Objective To analyze the relationship between Klotho promoter methylation of peripheral blood mononuclear cells （PBMC） and renal function in IgA nephropathy patients. Methods Seventy patients admitted to Zhongshan Hospital of Fudan University between August 2012 and February 2013 and diagnosed as primary IgA nephropathy by renal biopsy were included in this study. PBMC Klotho methylation revel was examined by pyrosequencing. The correlation between Klotho methylation and clinical indicators was analyzed. Results There were 39 men and 31 women with a mean age of （37.9± 11.8） years. The median of estimated glomerular filtration rate （eGFR） and PBMC Klotho promoter methylation rate were 49.2 （34.1,65.4） mL/（min 1. 73 m2） and 4.1% （2.7% ,6.0%）, respectively. PBMC Klotho methylation level was significantly lower in patients with eGFR〉 60 mL/（min · 1. 73 m2） than those with eGFR 30- 60 mL/（min. 1. 73m2） or eGFR 30 mL/（min-1, 73 m2）（2.7% [2.0%,2.8%] vs. 4.5% [3.5%,6.1%], 2.7% [2.0%,2.8%] vs. 6.9% [-5.5%,9.1%], 4.5% [3.5% ,6.1%] vs. 6.9% [5.5% ,9.1%], all P〈0.01）. Multiple regression analysis indicated that low eGFR was correlated significantly with high PBMC Klotho methylation level （β = - 0. 551, P〈 0.001）. Conclusion Elevated PBMC Klotho promoter methylation is associated with deterioration of renal function in IgA nephropathy patients.

关 键 词：IGA肾病 DNA甲基化 KLOTHO 肾小球滤过率 

分 类 号：R692.31[医药卫生—泌尿科学]