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

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