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NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition.

Publication ,  Journal Article
Mwinyi, J; Boström, AE; Pisanu, C; Murphy, SK; Erhart, W; Schafmayer, C; Hampe, J; Moylan, C; Schiöth, HB
Published in: Biochim Biophys Acta Mol Cell Biol Lipids
March 2017

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides, cholesterol and toxic free fatty acids and is related to low vitamin D levels. In an analysis of specific gene sets we elucidate to what extent NAFLD associates to epigenetic and related transcriptional changes in gene networks regulating lipid, energy and vitamin D balance. Two gene clusters responsible for lipid homeostasis (74 genes) and vitamin D and energy balance (31 genes) were investigated with regard to average epigenetic shifts within the first 1500bp next to the transcriptional start site. Three cohorts from two published genome wide driven studies that used a microarray approach were investigated including altogether 103 NAFLD and 75 liver healthy subjects. In the first two steps associations between NAFLD abundance, strength of fibrosis and methylation were investigated in two cohorts by multiple linear regression analyses, correcting for important clinical and demographic parameters. Methylation associated strength of transcription in genes showing significant NAFLD related methylation changes were studied in a third step using a third cohort and applying Pearson's correlation and robust linear regression analyses. 41 genes in gene cluster 1 and 14 genes in cluster 2 were significantly differentially methylated in dependency of NAFLD and hepatic fibrosis. We detect new genes significantly changed in methylation, including APO family members (lipid transport), NPC1L1, STARD (cholesterol transport) and GRHL (energy homeostasis). Our results allow novel insights into the hepatic epigenetic regulation of genes important for lipid and vitamin D balance in NAFLD.

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Published In

Biochim Biophys Acta Mol Cell Biol Lipids

DOI

ISSN

1388-1981

Publication Date

March 2017

Volume

1862

Issue

3

Start / End Page

314 / 323

Location

Netherlands

Related Subject Headings

  • Vitamin D
  • Triglycerides
  • Transcription, Genetic
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver
  • Lipoproteins
  • Humans
  • Homeostasis
 

Citation

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Chicago
ICMJE
MLA
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Mwinyi, J., Boström, A. E., Pisanu, C., Murphy, S. K., Erhart, W., Schafmayer, C., … Schiöth, H. B. (2017). NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition. Biochim Biophys Acta Mol Cell Biol Lipids, 1862(3), 314–323. https://doi.org/10.1016/j.bbalip.2016.12.005
Mwinyi, Jessica, Adrian E. Boström, Claudia Pisanu, Susan K. Murphy, Wiebke Erhart, Clemens Schafmayer, Jochen Hampe, Cynthia Moylan, and Helgi B. Schiöth. “NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition.Biochim Biophys Acta Mol Cell Biol Lipids 1862, no. 3 (March 2017): 314–23. https://doi.org/10.1016/j.bbalip.2016.12.005.
Mwinyi J, Boström AE, Pisanu C, Murphy SK, Erhart W, Schafmayer C, et al. NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition. Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Mar;1862(3):314–23.
Mwinyi, Jessica, et al. “NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition.Biochim Biophys Acta Mol Cell Biol Lipids, vol. 1862, no. 3, Mar. 2017, pp. 314–23. Pubmed, doi:10.1016/j.bbalip.2016.12.005.
Mwinyi J, Boström AE, Pisanu C, Murphy SK, Erhart W, Schafmayer C, Hampe J, Moylan C, Schiöth HB. NAFLD is associated with methylation shifts with relevance for the expression of genes involved in lipoprotein particle composition. Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Mar;1862(3):314–323.
Journal cover image

Published In

Biochim Biophys Acta Mol Cell Biol Lipids

DOI

ISSN

1388-1981

Publication Date

March 2017

Volume

1862

Issue

3

Start / End Page

314 / 323

Location

Netherlands

Related Subject Headings

  • Vitamin D
  • Triglycerides
  • Transcription, Genetic
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Male
  • Liver
  • Lipoproteins
  • Humans
  • Homeostasis