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@ARTICLE{Florath:125828,
      author       = {I. Florath$^*$ and K. Butterbach$^*$ and J. Heiss$^*$ and
                      M. Bewerunge-Hudler$^*$ and Y. Zhang$^*$ and B.
                      Schöttker$^*$ and H. Brenner$^*$},
      title        = {{T}ype 2 diabetes and leucocyte {DNA} methylation: an
                      epigenome-wide association study in over 1,500 older
                      adults.},
      journal      = {Diabetologia},
      volume       = {59},
      number       = {1},
      issn         = {1432-0428},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-01952},
      pages        = {130 - 138},
      year         = {2016},
      abstract     = {Development of type 2 diabetes depends on environmental and
                      genetic factors. We investigated the epigenome-wide
                      association of prevalent diabetes with DNA methylation
                      (DNAm) in peripheral blood.DNAm was measured in whole blood
                      with the Illumina Infinium HumanMethylation450 BeadChip in
                      two subsamples of participants from the ESTHER cohort study.
                      Cohort 1 included 988 participants, who were consecutively
                      recruited between July and October 2000 and cohort 2
                      included 527 randomly selected participants. The association
                      of DNAm with prevalent type 2 diabetes at recruitment was
                      estimated using median regression analysis adjusting for
                      sex, age, BMI, smoking behaviour, cell composition and batch
                      at 361,922 CpG sites.Type 2 diabetes was prevalent in $16\%$
                      of the participants, and diabetes was poorly controlled in
                      $45\%$ of the diabetic patients. In cohort 1 (discovery)
                      DNAm at 39 CpGs was significantly associated with prevalent
                      diabetes after correction for multiple testing. In cohort 2
                      (replication) at one of these CpGs, DNAm was still
                      significantly associated. Decreasing methylation levels at
                      cg19693031 with increasing fasting glucose and HbA1c
                      concentrations were observed using restricted cubic spline
                      analysis. In diabetic patients with poorly controlled
                      diabetes, the decrease in estimated DNAm levels was
                      approximately $5\%$ in comparison with participants free of
                      diagnosed diabetes.Cg19693031, which is located within the
                      3-untranslated region of TXNIP, might play a role in the
                      pathophysiology of type 2 diabetes. This result appears
                      biologically plausible given that thioredoxin-interacting
                      protein is overexpressed in diabetic animals and humans and
                      3-untranslated regions are known to play a regulatory role
                      in gene expression.},
      keywords     = {3' Untranslated Regions (NLM Chemicals) / Blood Glucose
                      (NLM Chemicals) / Carrier Proteins (NLM Chemicals) / TXNIP
                      protein, human (NLM Chemicals)},
      cin          = {C070 / W110 / G110 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)W110-20160331 /
                      I:(DE-He78)G110-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26433941},
      doi          = {10.1007/s00125-015-3773-7},
      url          = {https://inrepo02.dkfz.de/record/125828},
}