Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Silbernagel, G; Renner, W; Grammer, TB; Hugl, SR; Bertram, J; Kleber, ME; Hoffmann, MM; Winkelmann, BR; Marz, W; Boehm, BO.
Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon-like peptide 1
DIABETES-METAB RES. 2011; 27(5): 499-505.
Doi: 10.1002/dmrr.1194
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- Führende Autor*innen der Med Uni Graz
- Silbernagel Günther
- Co-Autor*innen der Med Uni Graz
- März Winfried
- Renner Wilfried
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- Abstract:
- Variants in TCF7L2 have been associated with the age at onset of type 2 diabetes in Mexican Americans. However, there is a lack of data on this relationship in Caucasians. Furthermore, risk alleles in TCF7L2 have been suggested to account for decreased conversion of proinsulin to insulin and decreased expression of GLP-1. We investigated the effect of the allelic variants rs1225537 and rs7903146 in TCF7L2 on the age at onset of type 2 diabetes, the plasma concentrations of proinsulin and GLP-1, and the ratio of proinsulin to insulin in a German cohort. We studied 3185 participants of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. Among these, 1021 subjects had type 2 diabetes. Data on age at onset of diabetes were available in 925 subjects. OGTTs were performed in a subgroup not previously known to have diabetes. Carriers of the risk alleles in rs1225537 and rs7901346 had increased risk of type 2 diabetes and elevated HbA(1c) (all p < 0.001). The risk alleles were also associated with early onset of type 2 diabetes, decreased insulin secretion and markedly increased proinsulin and proinsulin to insulin ratio (all p < 0.03). GLP-1 was not significantly related to the TCF7L2 genotype. Our data demonstrate that TCF7L2 variants are associated with an early age of onset of type 2 diabetes in Caucasians and affects the conversion of proinsulin to insulin. However, TCF7L2 is not consistently associated with fasting GLP-1. Copyright © 2011 John Wiley & Sons, Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- Age of Onset -
- Aged -
- Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - genetics
- European Continental Ancestry Group - genetics
- Female -
- Glucagon-Like Peptide 1 - blood
- Glucose Tolerance Test -
- Hemoglobin A, Glycosylated - analysis
- Humans -
- Insulin - blood Insulin - secretion
- Male -
- Middle Aged -
- Polymorphism, Single Nucleotide -
- Proinsulin - blood
- Risk -
- Transcription Factor 7-Like 2 Protein - genetics
- Find related publications in this database (Keywords)
- TCF7L2
- rs1225537
- rs7901346
- SNP
- type 2 diabetes
- age at onset
- insulin
- proinsulin
- GLP-1