Wing Maria R, Devaney Joseph M, Joffe Marshall M, Xie Dawei, Feldman Harold I, Dominic Elizabeth A, Guzman Nicolas J, Ramezani Ali, Susztak Katalin, Herman James G, Cope Leslie, Harmon Brennan, Kwabi-Addo Bernard, Gordish-Dressman Heather, Go Alan S, He Jiang, Lash James P, Kusek John W, Raj Dominic S
Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA.
Nephrol Dial Transplant. 2014 Apr;29(4):864-72. doi: 10.1093/ndt/gft537. Epub 2014 Feb 9.
Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD).
We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate.
The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD.
Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.
表观遗传机制可能在慢性肾脏病（CKD）进展中起重要作用。
我们使用Infinium HumanMethylation 450 K BeadChip对40名慢性肾功能不全（CRIC）研究参与者（n = 3939）进行了全基因组DNA甲基化模式研究，这些参与者的估计肾小球滤过率下降速率最高和最低。
稳定肾功能组和快速进展组的平均估算肾小球滤过率斜率分别为2.2（1.4）和-5.1（1.2）mL/min/1.73 m²。在肾功能稳定的受试者中，NPHP4、IQSEC1和TCF3中的CpG岛甲基化程度更高（P值为7.8E-05至9.5E-05）。这些基因参与已知促进上皮-间质转化和肾纤维化的途径。其他差异甲基化的CKD相关基因是NOS3、NFKBIL2、CLU、NFKBIB、TGFB3和TGFBI，它们参与氧化应激和炎症途径（P值为4.5E-03至0.046）。使用Ingenuity Pathway Analysis进行的通路分析表明，与细胞信号传导、碳水化合物代谢和人类行为相关的基因网络在CKD中受到表观遗传调控。
表观遗传修饰可能在确定已确诊CKD患者的肾功能丧失速率中起重要作用。
