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

Mwinyi, Jessica, (författare)
Uppsala universitet, Funktionell farmakologi
Boström, Adrian, (författare)
Uppsala universitet, Funktionell farmakologi
Pisanu, Claudia, (författare)
Uppsala universitet, Funktionell farmakologi, Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
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Murphy, Susan K., (författare)
Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA.
Erhart, Wiebke, (författare)
Univ Hosp Schleswig Holstein, Dept Internal Med 1, Kiel, Germany.
Schafmayer, Clemens, (författare)
Univ Hosp Schleswig Holstein, Dept Gen Surg & Thorac Surg, Kiel, Germany.
Hampe, Jochen, (författare)
Univ Hosp Dresden, Dept Med 1, Dresden, Germany.
Moylan, Cynthia, (författare)
Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.;Durham Vet Affairs Med Ctr, Dept Med, Durham, NC USA.
Schiöth, Helgi B., (författare)
Uppsala universitet, Funktionell farmakologi
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - 1388-1981 .- 1879-2618. ; 1862:3, s. 314-323
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
  • <p>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 1500 bp 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.</p>


MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)


Lipid and lipoprotein metabolism

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