Plasma Metabolomics Reveal Alterations of Sphingo- and Glycerophospholipid Levels in Non-Diabetic Carriers of the Transcription Factor 7-Like 2 Polymorphism rs7903146
| Autor: | Melina Claussnitzer, Christa Meisinger, Andreas Lechner, Anna Kirchhofer, Harald Grallert, Barbara Thorand, Cornelia Huth, Susanne M. Krug, Cornelia Then, Ina Heukamp, Margit Heier, Werner Römisch-Margl, Helmut Laumen, Gabi Kastenmüller, Jochen Seissler, Hans Hauner, Cornelia Prehn, Jerzy Adamski, Simone Wahl, Annette Peters, Thomas Illig |
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| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
Male endocrine system Genotype endocrine system diseases Science Glycerophospholipids Type 2 diabetes Biology Transcription Factor 7-Like 2 chemistry.chemical_compound Metabolomics medicine Humans Insulin ddc:610 Allele Gene Transcription factor Alleles Genetics Polymorphism Genetic Multidisciplinary nutritional and metabolic diseases Glucose Tolerance Test Middle Aged medicine.disease Sphingomyelins Diabetes Mellitus Type 2 chemistry Glycerophospholipid Metabolome Phosphatidylcholines Medicine lipids (amino acids peptides and proteins) Transcription Factor 7-Like 2 Protein TCF7L2 Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 10, p e78430 (2013) PLoS ONE 8:e78430 (2013) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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