Department of Pathology and Laboratory Medicine, Temple University Medical School, Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA, USA.
Epigenetics. 2011 Jan;6(1):20-8. doi: 10.4161/epi.6.1.13362. Epub 2011 Jan 1.
We identified potential epigenetic biomarkers for chronic kidney disease progression by comparing site-specific DNA methylation levels in more than 14,000 genes between African American and Hispanic diabetes patients with end stage renal disease (ESRD) and diabetes patients without nephropathy. We identified 187 genes that are differentially methylated between the two groups on at least two CpG sites in each gene in DNA extracted from saliva. Of the 187 genes whose mean methylation levels differed between the two groups, 39 genes, or closely related gene family members, have been reported to be involved in kidney development or diabetic nephropathy, per se, or have been associated with dialysis-induced changes in gene expression in peripheral blood cells. The fact that such a substantial fraction (21%) of the 187 candidate genes have been implicated previously through genome association or transcription profiling studies suggests strongly that the DNA methylation differences we observe are associated with disease predisposition and/or treatment. The fact that these nephropathy and/or dialysis-associated differences between patients were identified in DNA extracted from saliva offers proof-of-principle that inter-individual epigenetic differences may prove useful as predictive biomarkers of disease susceptibility.
我们通过比较非洲裔美国人和西班牙裔糖尿病终末期肾病 (ESRD) 患者与无肾病糖尿病患者在超过 14000 个基因中特定部位的 DNA 甲基化水平，确定了慢性肾脏病进展的潜在表观遗传生物标志物。我们在从唾液中提取的 DNA 中每个基因的至少两个 CpG 位点上鉴定出 187 个在两组之间存在差异甲基化的基因。在两组之间平均甲基化水平不同的 187 个基因中，有 39 个基因或密切相关的基因家族成员，据报道与肾脏发育或糖尿病肾病本身有关，或者与外周血细胞中透析诱导的基因表达变化有关。事实上，我们观察到的 DNA 甲基化差异与疾病易感性和/或治疗有关，这一事实强烈表明，在通过全基因组关联或转录谱研究已经涉及到如此大比例（21%）的 187 个候选基因。事实上，在从唾液中提取的 DNA 中鉴定出患者之间的这些与肾病和/或透析相关的差异，证明了个体间表观遗传差异可能作为疾病易感性的预测生物标志物是有道理的。
