PLoS ONE (Jan 2013)

Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.

  • Cornelia Then,
  • Simone Wahl,
  • Anna Kirchhofer,
  • Harald Grallert,
  • Susanne Krug,
  • Gabi Kastenmüller,
  • Werner Römisch-Margl,
  • Melina Claussnitzer,
  • Thomas Illig,
  • Margit Heier,
  • Christa Meisinger,
  • Jerzy Adamski,
  • Barbara Thorand,
  • Cornelia Huth,
  • Annette Peters,
  • Cornelia Prehn,
  • Ina Heukamp,
  • Helmut Laumen,
  • Andreas Lechner,
  • Hans Hauner,
  • Jochen Seissler

DOI
https://doi.org/10.1371/journal.pone.0078430
Journal volume & issue
Vol. 8, no. 10
p. e78430

Abstract

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Aims/hypothesisPolymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant.MethodsSeventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry.ResultsTCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6).DiscussionPlasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance.