Preserving Treg Function: Beyond mTOR Inhibitors.
Preserving Treg Function: Beyond mTOR Inhibitors.
复制标题
保留 Treg 功能：超越 mTOR 抑制剂。
DOI：
10.1097/tp.0000000000002042
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发表时间：
2018
期刊：
影响因子：
6.2
通讯作者：
Adigbli G
中科院分区：
文献类型：
--
作者：
Adigbli G
Chronic kidney disease (CKD) is often familial. Only a small part of these diseases are classical monogenic, environmental factors and DNA sequence variants play a major role in the development of CKD. Epigenomewide association studies have identified more than 60 genetic loci associated with CKD. Altered transcriptional regulation due to epigenetic changes has a major role in DNA methylation influencing the incidence of CKD and its progression. Cu and coworkers formulated 3 aims for their study:(i) to use epigenomewide association studies for the discovery and validation of genomewide differences in DNA methylation at CpG sites (CpGs) that is present in patients with CKD;(ii) to characterize these validated CpGs in kidney tissue; and (iii) lastly, to link differential DNA methylation to compromised kidney function. The authors enrolled 2264 African American patients from the Atherosclerosis Risk in Communities Study and 2595 European ancestry participants form the Framingham Heart Study. DNA methylation at> 440 000 CgGs were examined in whole blood. In the Atherosclerosis Risk in Communities study 16 CpGs were associated with prevalent CKD, while 11 CpGs were associated with prevalent CKD in the Framingham Heart Study. In total, 5 CpGs were associated with a degree of fibrosis in kidney biopsies, a pathological correlation with CKD.Next, DNA methylation sites were quantified from the cortical tubule portion of 95 microdissected human kidney samples to investigate whether the CpG associations in whole blood translated to kidney tissue. Of the 19 replicated CpGs, 5 showed significant association with renal fibrosis. This well-powered study has identified important target genes for future mechanistic and therapeutic strategies of CKD.
