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Sökning: WFRF:(Rönn Tina) > Pihlajamäki Jussi

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1.
  • Bysani, Madhusudhan, et al. (författare)
  • Epigenetic alterations in blood mirror age-associated DNA methylation and gene expression changes in human liver
  • 2017
  • Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 9:2, s. 105-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To study the impact of aging on DNA methylation and mRNA expression in human liver. Experimental procedures: We analysed genome-wide DNA methylation and gene expression in human liver samples using Illumina 450K and HumanHT12 expression BeadChip arrays. Results: DNA methylation analysis of ∼455,000 CpG sites in human liver revealed that age was significantly associated with altered DNA methylation of 20,396 CpG sites. Comparison of liver methylation data with published methylation data in other tissues showed that vast majority of the age-associated significant CpG sites overlapped between liver and blood, whereas a smaller overlap was found between liver and pancreatic islets or adipose tissue, respectively. We identified 151 genes whose liver expression also correlated with age. Conclusions: We identified age-associated DNA methylation and expression changes in human liver that are partly reflected by epigenetic alterations in blood.
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2.
  • de Mello, Vanessa, et al. (författare)
  • Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action
  • 2017
  • Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 12:4, s. 287-295
  • Tidskriftsartikel (refereegranskat)abstract
    • Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m2, type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q < 0.001), independently of T2D, age, sex, and BMI. Focusing on the top-ranking 30 and another 37 CpG sites mapped to genes enriched in pathways of metabolism (q = 0.0036) and cancer (q = 0.0001) all together, 59 NASH-associated CpG sites correlated with fasting insulin levels independently of age, fasting glucose, or T2D. From these, we identified 30 correlations between DNA methylation and mRNA expression, for example LDHB (r = −0.45, P = 0.003). We demonstrated that NASH, more than simple steatosis, associates with differential DNA methylation in the human liver. These epigenetic alterations in NASH are linked with insulin metabolism.
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  • Resultat 1-2 av 2
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tidskriftsartikel (2)
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refereegranskat (2)
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Nilsson, Emma (2)
Perfilyev, Alexander (2)
Rönn, Tina (2)
Ling, Charlotte (2)
de Mello, Vanessa (2)
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Bysani, Madhusudhan (1)
Männistö, Ville (1)
Matte, Ashok (1)
Käkelä, Pirjo (1)
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Lunds universitet (2)
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Engelska (2)
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Medicin och hälsovetenskap (2)
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