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

PLoS ONE 8:e78430 (2013)
Publishers Version DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
as soon as is submitted to ZB.
Aims/Hypothesis Polymorphisms 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. Methods Seventeen 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. Results TCF7L2 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).
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Publication type Article: Journal article
Document type Scientific Article
Keywords Type-2 Diabetes-mellitus ; Secretory Phospholipase A(2) ; Scale Association Analysis ; Insulin-resistance ; Tcf7l2 Gene ; Adipose-tissue ; Risk ; Metabolism ; Acid ; Increases
Reviewing status
Institute(s) Institute of Experimental Genetics (IEG)
CCG Biomarker for the subclassification of T2DM (KKG-KDB)
Research Unit Molecular Epidemiology (AME)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Epidemiology II (EPI2)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)