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IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits

Rohde, Kerstin LU ; Klös, Matthias; Hopp, Lydia; Liu, Xuanshi; Keller, Maria LU ; Stumvoll, Michael; Dietrich, Arne; Schön, Michael R.; Gärtner, Daniel and Lohmann, Tobias, et al. (2017) In Scientific Reports 7(1).
Abstract

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10-6), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT... (More)

The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10-6), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT and SAT methylation correlated negatively with IRS1 gene expression in obese subjects (N = 16, P = 0.007 and P = 0.010). The major T-allele is related to increased DNA methylation in OVAT (N = 146, P = 0.019). Finally, DNA methylation and gene expression in OVAT correlated with anthropometric traits (waist- circumference waist-to-hip ratio) and parameters of glucose metabolism in obese individuals. Our data suggest that the association between rs2943650 near the IRS1 gene locus with clinically relevant variables may at least be modulated by changes in DNA methylation that translates into altered IRS1 gene expression.

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published
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in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85030087527
ISSN
2045-2322
DOI
10.1038/s41598-017-12393-5
language
English
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no
id
3aa2083e-67ed-4fdf-b159-7584194fa78e
date added to LUP
2017-10-10 10:35:40
date last changed
2018-01-10 03:00:14
@article{3aa2083e-67ed-4fdf-b159-7584194fa78e,
  abstract     = {<p>The SNP variant rs2943650 near IRS1 gene locus was previously associated with decreased body fat and IRS1 gene expression as well as an adverse metabolic profile in humans. Here, we hypothesize that these effects may be mediated by an interplay with epigenetic alterations. We measured IRS1 promoter DNA methylation and mRNA expression in paired human subcutaneous and omental visceral adipose tissue samples (SAT and OVAT) from 146 and 41 individuals, respectively. Genotyping of rs2943650 was performed in all individuals (N = 146). We observed a significantly higher IRS1 promoter DNA methylation in OVAT compared to SAT (N = 146, P = 8.0 × 10<sup>-6</sup>), while expression levels show the opposite effect direction (N = 41, P = 0.011). OVAT and SAT methylation correlated negatively with IRS1 gene expression in obese subjects (N = 16, P = 0.007 and P = 0.010). The major T-allele is related to increased DNA methylation in OVAT (N = 146, P = 0.019). Finally, DNA methylation and gene expression in OVAT correlated with anthropometric traits (waist- circumference waist-to-hip ratio) and parameters of glucose metabolism in obese individuals. Our data suggest that the association between rs2943650 near the IRS1 gene locus with clinically relevant variables may at least be modulated by changes in DNA methylation that translates into altered IRS1 gene expression.</p>},
  articleno    = {12369},
  author       = {Rohde, Kerstin and Klös, Matthias and Hopp, Lydia and Liu, Xuanshi and Keller, Maria and Stumvoll, Michael and Dietrich, Arne and Schön, Michael R. and Gärtner, Daniel and Lohmann, Tobias and Dreßler, Miriam and Kovacs, Peter and Binder, Hans and Blüher, Matthias and Böttcher, Yvonne},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {IRS1 DNA promoter methylation and expression in human adipose tissue are related to fat distribution and metabolic traits},
  url          = {http://dx.doi.org/10.1038/s41598-017-12393-5},
  volume       = {7},
  year         = {2017},
}