Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation

Saurabh Baheti; Prachi Singh; Yun Zhang; Jared Evans; Michael D. Jensen; Virend K. Somers; Jean Pierre A. Kocher; Zhifu Sun; Harini A. Chakkera

doi:10.2217/epi-2017-0050

Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation

Saurabh Baheti, Prachi Singh, Yun Zhang, Jared Evans, Michael D. Jensen, Virend K. Somers, Jean Pierre A. Kocher, Zhifu Sun, Harini A. Chakkera

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied. Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations. Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.

Original language	English (US)
Pages (from-to)	1423-1435
Number of pages	13
Journal	Epigenomics
Volume	9
Issue number	11
DOIs	https://doi.org/10.2217/epi-2017-0050
State	Published - Nov 2017

Keywords

DNA methylation
RRBS
adipose tissue
new-onset diabetes after transplant

ASJC Scopus subject areas

Genetics
Cancer Research

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10.2217/epi-2017-0050

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title = "Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation",

abstract = "Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied. Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations. Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.",

keywords = "DNA methylation, RRBS, adipose tissue, new-onset diabetes after transplant",

author = "Saurabh Baheti and Prachi Singh and Yun Zhang and Jared Evans and Jensen, {Michael D.} and Somers, {Virend K.} and Kocher, {Jean Pierre A.} and Zhifu Sun and Chakkera, {Harini A.}",

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doi = "10.2217/epi-2017-0050",

language = "English (US)",

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pages = "1423--1435",

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T1 - Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation

AU - Baheti, Saurabh

AU - Singh, Prachi

AU - Zhang, Yun

AU - Evans, Jared

AU - Jensen, Michael D.

AU - Somers, Virend K.

AU - Kocher, Jean Pierre A.

AU - Sun, Zhifu

AU - Chakkera, Harini A.

PY - 2017/11

Y1 - 2017/11

N2 - Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied. Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations. Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.

AB - Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role. Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied. Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations. Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.

KW - DNA methylation

KW - RRBS

KW - adipose tissue

KW - new-onset diabetes after transplant

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Adipose tissue DNA methylome changes in development of new-onset diabetes after kidney transplantation

Abstract

Keywords

ASJC Scopus subject areas

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