Department of Internal Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea.
Medical Science Research Center, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea.
Genes (Basel). 2023 Jul 21;14(7):1489. doi: 10.3390/genes14071489.
Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development.
We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period ("CKD prediction" analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years ("kidney function slope" analysis).
In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, , , and , were found to be significant in the CKD prediction analysis and related to a decline in kidney function.
It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function.
尽管人们对影响肾脏疾病的遗传因素的了解在不断增加，但与慢性肾脏病（CKD）相关的表观遗传谱尚未得到充分阐明。我们试图确定与肾功能下降相关的 CpG 位点的 DNA 甲基化状态，并研究鉴定出的 CpG 位点是否与 CKD 的发生有关。
我们分析了韩国基因组与流行病学研究（KoGES）中 440 名基线估计肾小球滤过率（eGFR）≥60mL/min/1.73m 的参与者的 DNA 甲基化模式。在 8 年的随访期间，任何时候 eGFR 下降<60 被定义为 CKD 进展（“CKD 预测”分析）。此外，在这 440 名参与者中，对 49 名接受第二次甲基化分析的参与者进行了肾功能下降与 8 年内 CpG 位点甲基化程度变化之间的相关性评估（“肾功能斜率”分析）。
在 CKD 预测分析中，对 440 名参与者的基线进行了总计 403129 个 CpG 位点的甲基化分析，多元逻辑回归显示，268 个 CpG 位点的甲基化增加和 189 个 CpG 位点的甲基化减少与 CKD 的发生显著相关。在对 49 名参与者的随访甲基化分析进行肾功能斜率分析时，913 个 CpG 位点的甲基化百分比变化与 8 年内 eGFR 的变化呈线性关系。在对 CKD 预测和肾功能斜率分析中发现的有意义的 CpG 位点的功能富集分析中，我们发现这些 CpG 位点代表了 MAPK、PI3K/Akt 和 Rap1 途径。此外，三个基因中的三个 CpG 位点， ， ，和 ，在 CKD 预测分析中具有统计学意义，与肾功能下降有关。
提示特定基因的 DNA 甲基化与 CKD 的发生和肾功能的恶化有关。
