Kidney cytosine methylation changes improve renal function decline estimation in patients with diabetic kidney disease

被引：56

作者：

Gluck, Caroline ^{[1
,2
]}

Qiu, Chengxiang ^{[1
]}

Han, Sang Youb ^{[3
]}

Palmer, Matthew ^{[4
]}

Park, Jihwan ^{[1
]}

Ko, Yi-An ^{[1
,5
]}

Guan, Yuting ^{[1
]}

Sheng, Xin ^{[1
]}

Hanson, Robert L. ^{[6
]}

Huang, Jing ^{[7
]}

Chen, Yong ^{[7
]}

Park, Ae Seo Deok ^{[1
]}

Izquierdo, Maria Concepcion ^{[1
]}

Mantzaris, Ioannis ^{[8
]}

Verma, Amit ^{[8
]}

Pullman, James ^{[9
]}

Li, Hongzhe ^{[7
]}

Susztak, Katalin ^{[1
,5
]}

机构：

[1] Univ Penn, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA

[2] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pediat,Div Nephrol, Philadelphia, PA 19104 USA

[3] Inje Univ, Coll Med, Div Nephrol, Dept Internal Med, Goyang 10380, South Korea

[4] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[6] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 86014 USA

[7] Univ Penn Perelman, Dept Biostat Epidemiol & Informat, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA

[8] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA

[9] Montefiore Med Ctr, Dept Pathol, Bronx, NY 10467 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

EPIGENOME-WIDE ASSOCIATION; DNA METHYLATION; BLOOD-PRESSURE; METABOLIC MEMORY; PROGRESSION; COMPLICATIONS; EPIGENETICS; DISCOVERY; OUTCOMES; GENES;

D O I：

10.1038/s41467-019-10378-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epigenetic changes might provide the biological explanation for the long-lasting impact of metabolic alterations of diabetic kidney disease development. Here we examined cytosine methylation of human kidney tubules using Illumina Infinium 450 K arrays from 91 subjects with and without diabetes and varying degrees of kidney disease using a cross-sectional design. We identify cytosine methylation changes associated with kidney structural damage and build a model for kidney function decline. We find that the methylation levels of 65 probes are associated with the degree of kidney fibrosis at genome wide significance. In total 471 probes improve the model for kidney function decline. Methylation probes associated with kidney damage and functional decline enrich on kidney regulatory regions and associate with gene expression changes, including epidermal growth factor (EGF). Altogether, our work shows that kidney methylation differences can be detected in patients with diabetic kidney disease and improve kidney function decline models indicating that they are potentially functionally important.

引用

页数：12

共 70 条

[1] The association between methylation levels of targeted genes and albuminuria in patients with early diabetic kidney disease
Aldemir, Ozgur
Turgut, Faruk
Gokce, Cumali
[J]. RENAL FAILURE, 2017, 39 (01) : 597 - 601
[2] Extracting replicable associations across multiple studies: Empirical Bayes algorithms for controlling the false discovery rate
Amar, David
Shamir, Ron
Yekutieli, Daniel
[J]. PLOS COMPUTATIONAL BIOLOGY, 2017, 13 (08) : e1005700
[3] Time-Updated Systolic Blood Pressure and the Progression of Chronic Kidney Disease A Cohort Study
Anderson, Amanda H.
Yang, Wei
Townsend, Raymond R.
Pan, Qiang
Chertow, Glenn M.
Kusek, John W.
Charleston, Jeanne
He, Jiang
Kallem, RadhaKrishna
Lash, James P.
Miller, Edgar R., III
Rahman, Mahboob
Steigerwalt, Susan
Weir, Matthew
Wright, Jackson T., Jr.
Feldman, Harold I.
[J]. ANNALS OF INTERNAL MEDICINE, 2015, 162 (04) : 258 - +
[4] "Gap hunting" to characterize clustered probe signals in Illumina methylation array data
Andrews, Shan V.
Ladd-Acosta, Christine
Feinberg, Andrew P.
Hansen, Kasper D.
Fallin, M. Daniele
[J]. EPIGENETICS & CHROMATIN, 2016, 9 : 1 - 21
[5] [Anonymous], 2020, Nat Rev Dis Primers, DOI DOI 10.1038/NRDP.2015.18
[6] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
Ardlie, Kristin G.
DeLuca, David S.
Segre, Ayellet V.
Sullivan, Timothy J.
Young, Taylor R.
Gelfand, Ellen T.
Trowbridge, Casandra A.
Maller, Julian B.
Tukiainen, Taru
Lek, Monkol
Ward, Lucas D.
Kheradpour, Pouya
Iriarte, Benjamin
Meng, Yan
Palmer, Cameron D.
Esko, Tonu
Winckler, Wendy
Hirschhorn, Joel N.
Kellis, Manolis
MacArthur, Daniel G.
Getz, Gad
Shabalin, Andrey A.
Li, Gen
Zhou, Yi-Hui
Nobel, Andrew B.
Rusyn, Ivan
Wright, Fred A.
Lappalainen, Tuuli
Ferreira, Pedro G.
Ongen, Halit
Rivas, Manuel A.
Battle, Alexis
Mostafavi, Sara
Monlong, Jean
Sammeth, Michael
Mele, Marta
Reverter, Ferran
Goldmann, Jakob M.
Koller, Daphne
Guigo, Roderic
McCarthy, Mark I.
Dermitzakis, Emmanouil T.
Gamazon, Eric R.
Im, Hae Kyung
Konkashbaev, Anuar
Nicolae, Dan L.
Cox, Nancy J.
Flutre, Timothee
Wen, Xiaoquan
Stephens, Matthew
[J]. SCIENCE, 2015, 348 (6235) : 648 - 660
[7] Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays
Aryee, Martin J.
Jaffe, Andrew E.
Corrada-Bravo, Hector
Ladd-Acosta, Christine
Feinberg, Andrew P.
Hansen, Kasper D.
Irizarry, Rafael A.
[J]. BIOINFORMATICS, 2014, 30 (10) : 1363 - 1369
[8] Assenov Y, 2014, NAT METHODS, V11, P1138, DOI [10.1038/NMETH.3115, 10.1038/nmeth.3115]
[9] GROWTH INUTERO, BLOOD-PRESSURE IN CHILDHOOD AND ADULT LIFE, AND MORTALITY FROM CARDIOVASCULAR-DISEASE
BARKER, DJP
OSMOND, C
GOLDING, J
KUH, D
WADSWORTH, MEJ
[J]. BRITISH MEDICAL JOURNAL, 1989, 298 (6673) : 564 - 567
[10] Human Kidney Tubule-Specific Gene Expression Based Dissection of Chronic Kidney Disease Traits
Beckerman, Pazit
Qiu, Chengxiang
Park, Jihwan
Ledo, Nora
Ko, Yi-An
Park, Ae-Seo Deok
Han, Sang-Youb
Choi, Peter
Palmer, Matthew
Susztak, Katalin
[J]. EBIOMEDICINE, 2017, 24 : 267 - 276

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