Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon-like peptide 1

作者：Silbernagel Guenther; Renner Wilfried; Grammer Tanja B; Huegl Sigrun R; Bertram Julia; Kleber Marcus E; Hoffmann Michael M; Winkelmann Bernhard R; Maerz Winfried; Boehm Bernhard O^*

来源：Diabetes/Metabolism Research and Reviews, 2011, 27(5): 499-505.

DOI：10.1002/dmrr.1194

• TCF7L2
• rs1225537
• rs7901346
• SNP
• type 2 diabetes
• age at onset
• insulin
• proinsulin
• GLP-1

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.

• 出版日期2011-7
• 单位河北医科大学