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

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

<h4>Aims/hypothesis</h4>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.<h4>Method...

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Autores principales: 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
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:10dcb9f87dc441918c7b7b91ac273b052021-11-18T08:49:36ZPlasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.1932-620310.1371/journal.pone.0078430https://doaj.org/article/10dcb9f87dc441918c7b7b91ac273b052013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24205231/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Discussion</h4>Plasma 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.Cornelia ThenSimone WahlAnna KirchhoferHarald GrallertSusanne KrugGabi KastenmüllerWerner Römisch-MarglMelina ClaussnitzerThomas IlligMargit HeierChrista MeisingerJerzy AdamskiBarbara ThorandCornelia HuthAnnette PetersCornelia PrehnIna HeukampHelmut LaumenAndreas LechnerHans HaunerJochen SeisslerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e78430 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
description <h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Discussion</h4>Plasma 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.
format article
author 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
author_facet 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
author_sort Cornelia Then
title Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
title_short Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
title_full Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
title_fullStr Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
title_full_unstemmed Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
title_sort plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/10dcb9f87dc441918c7b7b91ac273b05
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