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

被引：15

作者：

Silbernagel, Guenther ^{[8
]}

Renner, Wilfried ^{[7
]}

Grammer, Tanja B. ^{[4
,5
]}

Huegl, Sigrun R. ^{[1
]}

Bertram, Julia ^{[1
]}

Kleber, Marcus E. ^{[2
,5
]}

Hoffmann, Michael M. ^{[3
]}

Winkelmann, Bernhard R. ^{[6
]}

Maerz, Winfried ^{[4
,5
,7
]}

Boehm, Bernhard O. ^{[1
]}

机构：

[1] Univ Ulm, Div Endocrinol, Dept Internal Med, D-89070 Ulm, Germany

[2] LURIC Study Nonprofit LLC, Freiburg, Germany

[3] Univ Med Ctr Freiburg, Div Clin Chem, Dept Internal Med, Freiburg, Germany

[4] Heidelberg Univ, Mannheim Med Fac, Inst Publ Hlth Social & Prevent Med, D-6800 Mannheim, Germany

[5] Synlab Ctr, Lab Diagnost Heidelberg, Heidelberg, Germany

[6] Cardiol Grp Frankfurt Sachsenhausen, Frankfurt, Germany

[7] Med Univ Graz, Diagnost Lab, Clin Inst Med & Chem, Graz, Austria

[8] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, D-7400 Tubingen, Germany

来源：

DIABETES-METABOLISM RESEARCH AND REVIEWS | 2011年 / 27卷 / 05期

关键词：

TCF7L2; rs1225537; rs7901346; SNP; type; 2; diabetes; age at onset; insulin; proinsulin; GLP-1; CONTEXT-SPECIFIC RISK; BETA-CELL FUNCTION; POLYMORPHISM RS7903146; ATHEROSCLEROSIS RISK; INSULIN SENSITIVITY; METABOLIC SYNDROME; CAUCASIAN ADULTS; AFRICAN-AMERICAN; GENE; GLUCOSE;

D O I：

10.1002/dmrr.1194

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (C) Copyright. 2011 John Wiley & Sons, Ltd.

引用

页码：499 / 505

页数：7

共 33 条

[1]

Am Diabetes Assoc, 2006, DIABETES CARE, V29, pS4

[2] Transcription factor TCF7L2 genetic study in the French population -: Expression in human β-cells and adipose tissue and strong association with type 2 diabetes [J].

Cauchi, Stephane ;

Meyre, David ;

Dina, Christian ;

Choquet, Helene ;

Samson, Chantal ;

Gallina, Sophie ;

Balkau, Beverley ;

Charpentier, Guillaume ;

Pattou, Francois ;

Stetsyuk, Volodymyr ;

Scharfmann, Raphael ;

Staels, Bart ;

Fruhbeck, Gema ;

Froguel, Philippe .

DIABETES, 2006, 55 (10) :2903-2908

[3] Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City [J].

Cruz, M. ;

Valladares-Salgado, A. ;

Garcia-Mena, J. ;

Ross, K. ;

Edwards, M. ;

Angeles-Martinez, J. ;

Ortega-Camarillo, C. ;

Escobedo de la Pena, J. ;

Burguete-Garcia, A. I. ;

Wacher-Rodarte, N. ;

Ambriz, R. ;

Rivera, R. ;

D'artote, A. L. ;

Peralta, J. ;

Parra, Esteban J. ;

Kumate, J. .

DIABETES-METABOLISM RESEARCH AND REVIEWS, 2010, 26 (04) :261-270

[4] Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish -: Replication and evidence for a role in both insulin secretion and insulin resistance [J].

Damcott, Coleen M. ;

Pollin, Toni I. ;

Reinhart, Laurie J. ;

Ott, Sandra H. ;

Shen, Haiqing ;

Silver, Kristi D. ;

Mitchell, Braxton D. ;

Shuldiner, Alan R. .

DIABETES, 2006, 55 (09) :2654-2659

[5] Transcription factor 7-like 2 polymorphisms and type 2 diabetes, glucose homeostasis traits and gene expression in US participants of European and African descent [J].

Elbein, S. C. ;

Chu, W. S. ;

Das, S. K. ;

Yao-Borengasser, A. ;

Hasstedt, S. J. ;

Wang, H. ;

Rasouli, N. ;

Kern, P. A. .

DIABETOLOGIA, 2007, 50 (08) :1621-1630

[6] Cubic exact solutions for the estimation of pairwise haplotype frequencies:: implications for linkage disequilibrium analyses and a web tool 'CubeX' [J].

Gaunt, Tom R. ;

Rodriguez, Santiago ;

Day, Ian N. M. .

BMC BIOINFORMATICS, 2007, 8 (1)

[7] Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population [J].

Gonzalez-Sanchez, J. L. ;

Martinez-Larrad, M. T. ;

Zabena, C. ;

Perez-Barba, M. ;

Serrano-Rios, M. .

DIABETOLOGIA, 2008, 51 (11) :1993-1997

[8] Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J].

Grant, SFA ;

Thorleifsson, G ;

Reynisdottir, I ;

Benediktsson, R ;

Manolescu, A ;

Sainz, J ;

Helgason, A ;

Stefansson, H ;

Emilsson, V ;

Helgadottir, A ;

Styrkarsdottir, U ;

Magnusson, KP ;

Walters, GB ;

Palsdottir, E ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Gylfason, A ;

Saemundsdottir, J ;

Wilensky, RL ;

Reilly, MP ;

Rader, DJ ;

Bagger, Y ;

Christiansen, C ;

Gudnason, V ;

Sigurdsson, G ;

Thorsteinsdottir, U ;

Gulcher, JR ;

Kong, A ;

Stefansson, K .

NATURE GENETICS, 2006, 38 (03) :320-323

[9] The risk allele load accelerates the age-dependent decline in beta cell function [J].

Haupt, A. ;

Staiger, H. ;

Schaefer, S. A. ;

Kirchhoff, K. ;

Guthoff, M. ;

Machicao, F. ;

Gallwitz, B. ;

Stefan, N. ;

Haring, H-U. ;

Fritsche, A. .

DIABETOLOGIA, 2009, 52 (03) :457-462

[10] Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 Genes Confer Risk of Type 2 Diabetes Independently of BMI in the German KORA Studies [J].

Herder, C. ;

Rathmann, W. ;

Strassburger, K. ;

Finner, H. ;

Grallert, H. ;

Huth, C. ;

Meisinger, C. ;

Gieger, C. ;

Martin, S. ;

Giani, G. ;

Scherbaum, W. A. ;

Wichmann, H. -E. ;

Illig, T. .

HORMONE AND METABOLIC RESEARCH, 2008, 40 (10) :722-726

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