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Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon‐like peptide 1
Author(s) -
Silbernagel Guenther,
Renner Wilfried,
Grammer Tanja B.,
Hügl Sigrun R.,
Bertram Julia,
Kleber Marcus E.,
Hoffmann Michael M.,
Winkelmann Bernhard R.,
März Winfried,
Boehm Bernhard O.
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1194
Subject(s) - proinsulin , tcf7l2 , medicine , endocrinology , insulin , type 2 diabetes , diabetes mellitus , prohormone , allele , single nucleotide polymorphism , genotype , biology , hormone , genetics , gene
Background 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. Methods 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. Results 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. Conclusions 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.