Nature communications · 2017
Epigenome-wide association studies identify DNA methylation associated with kidney function.
СтатьяResearch Support, American Recovery and Reinvestment ActПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Chu Audrey Y, Tin Adrienne, Schlosser Pascal, Ko Yi-An, Qiu Chengxiang, Yao Chen, Joehanes Roby, Grams Morgan E, Liang Liming, Gluck Caroline A, Liu Chunyu, Coresh Josef, Hwang Shih-Jen, Levy Daniel, Boerwinkle Eric, Pankow James S, Yang Qiong, Fornage Myriam, Fox Caroline S, Susztak Katalin, Köttgen Anna
Аннотация
Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.
Предметные рубрики MeSH
AgedBinding SitesCCAAT-Enhancer-Binding Protein-betaCpG IslandsDNA MethylationDisease ProgressionE1A-Associated p300 ProteinEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGlomerular Filtration RateHumansKidneyMaleMiddle AgedProhibitinsProspective StudiesProtein Tyrosine Phosphatase, Non-Receptor Type 6Renal Insufficiency, ChronicTrans-ActivatorsTranscription Factors