AIM/HYPOTHESIS: A strong association between susceptibility to type 2 diabetes and common variants of transcription factor 7-like 2 (TCF7L2), encoding an enteroendocrine transcription factor involved in glucose homeostasis, has been reported in three different populations (Iceland, Denmark and USA) by Grant et al. We aimed to replicate these findings in a Dutch cohort. METHODS: We analysed the genotypes of two intronic single nucleotide polymorphisms (SNPs) in TCF7L2 gene in 502 unrelated type 2 diabetes patients and in a set of healthy controls (n = 920). The two SNPs showed almost complete linkage disequilibrium (D' = 0.91). RESULTS: We were able to replicate the previously reported association in our Breda cohort. The minor alleles of both variants were significantly over-represented in cases (odds ratio [OR] 1.29, 95% CI 1.09-1.52, [Formula: see text] for rs12255372; OR 1.41, 95% CI 1.19-1.66, [Formula: see text] for rs7903146). In addition, TCF7L2 haplotypes were analysed for association with the disease. The analysis of haplotypes did not reveal any strong association beyond that expected from analysing individual SNPs. The TT haplotype carrying the minor alleles was more frequent among cases (OR 1.38, [Formula: see text]). CONCLUSIONS/ INTERPRETATION: Our data strongly confirm that variants of the TCF7L2 gene contribute to the risk of type 2 diabetes. The population-attributable risk from this factor in the Dutch type 2 diabetes population is 10%.
AIM/HYPOTHESIS: A strong association between susceptibility to type 2 diabetes and common variants of transcription factor 7-like 2 (TCF7L2), encoding an enteroendocrine transcription factor involved in glucose homeostasis, has been reported in three different populations (Iceland, Denmark and USA) by Grant et al. We aimed to replicate these findings in a Dutch cohort. METHODS: We analysed the genotypes of two intronic single nucleotide polymorphisms (SNPs) in TCF7L2 gene in 502 unrelated type 2 diabetespatients and in a set of healthy controls (n = 920). The two SNPs showed almost complete linkage disequilibrium (D' = 0.91). RESULTS: We were able to replicate the previously reported association in our Breda cohort. The minor alleles of both variants were significantly over-represented in cases (odds ratio [OR] 1.29, 95% CI 1.09-1.52, [Formula: see text] for rs12255372; OR 1.41, 95% CI 1.19-1.66, [Formula: see text] for rs7903146). In addition, TCF7L2 haplotypes were analysed for association with the disease. The analysis of haplotypes did not reveal any strong association beyond that expected from analysing individual SNPs. The TT haplotype carrying the minor alleles was more frequent among cases (OR 1.38, [Formula: see text]). CONCLUSIONS/ INTERPRETATION: Our data strongly confirm that variants of the TCF7L2 gene contribute to the risk of type 2 diabetes. The population-attributable risk from this factor in the Dutch type 2 diabetes population is 10%.
Authors: Struan F A Grant; Gudmar Thorleifsson; Inga Reynisdottir; Rafn Benediktsson; Andrei Manolescu; Jesus Sainz; Agnar Helgason; Hreinn Stefansson; Valur Emilsson; Anna Helgadottir; Unnur Styrkarsdottir; Kristinn P Magnusson; G Bragi Walters; Ebba Palsdottir; Thorbjorg Jonsdottir; Thorunn Gudmundsdottir; Arnaldur Gylfason; Jona Saemundsdottir; Robert L Wilensky; Muredach P Reilly; Daniel J Rader; Yu Bagger; Claus Christiansen; Vilmundur Gudnason; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Jeffrey R Gulcher; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2006-01-15 Impact factor: 38.330
Authors: Alienke J Monsuur; Paul I W de Bakker; Behrooz Z Alizadeh; Alexandra Zhernakova; Marianna R Bevova; Eric Strengman; Lude Franke; Ruben van't Slot; Martine J van Belzen; Ineke C M Lavrijsen; Begoña Diosdado; Mark J Daly; Chris J J Mulder; M Luisa Mearin; Jos W R Meijer; Gerrit A Meijer; Erica van Oort; Martin C Wapenaar; Bobby P C Koeleman; Cisca Wijmenga Journal: Nat Genet Date: 2005-11-13 Impact factor: 38.330
Authors: J H O van Tilburg; L A Sandkuijl; E Strengman; H van Someren; C A E Rigters-Aris; P L Pearson; T W van Haeften; C Wijmenga Journal: J Clin Endocrinol Metab Date: 2003-05 Impact factor: 5.958
Authors: Inga Reynisdottir; Gudmar Thorleifsson; Rafn Benediktsson; Gunnar Sigurdsson; Valur Emilsson; Anna Sigurlin Einarsdottir; Eyrun Edda Hjorleifsdottir; Gudbjorg Th Orlygsdottir; Gudrun Thora Bjornsdottir; Jona Saemundsdottir; Skarphedinn Halldorsson; Soffia Hrafnkelsdottir; Steinunn Bjorg Sigurjonsdottir; Svana Steinsdottir; Mitchell Martin; Jarema P Kochan; Brian K Rhees; Struan F A Grant; Michael L Frigge; Augustine Kong; Vilmundur Gudnason; Kari Stefansson; Jeffrey R Gulcher Journal: Am J Hum Genet Date: 2003-07-08 Impact factor: 11.025
Authors: S C Elbein; W S Chu; S K Das; A Yao-Borengasser; S J Hasstedt; H Wang; N Rasouli; P A Kern Journal: Diabetologia Date: 2007-06-20 Impact factor: 10.122
Authors: K Pilgaard; C B Jensen; J H Schou; V Lyssenko; L Wegner; C Brøns; T Vilsbøll; T Hansen; S Madsbad; J J Holst; A Vølund; P Poulsen; L Groop; O Pedersen; A A Vaag Journal: Diabetologia Date: 2009-03-14 Impact factor: 10.122
Authors: Nicholette D Palmer; Allison B Lehtinen; Carl D Langefeld; Joel K Campbell; Steven M Haffner; Jill M Norris; Richard N Bergman; Mark O Goodarzi; Jerome I Rotter; Donald W Bowden Journal: J Clin Endocrinol Metab Date: 2007-10-30 Impact factor: 5.958
Authors: Ludmila Prokunina-Olsson; Cullan Welch; Ola Hansson; Neeta Adhikari; Laura J Scott; Nicolle Usher; Maurine Tong; Andrew Sprau; Amy Swift; Lori L Bonnycastle; Michael R Erdos; Zhi He; Richa Saxena; Brennan Harmon; Olga Kotova; Eric P Hoffman; David Altshuler; Leif Groop; Michael Boehnke; Francis S Collins; Jennifer L Hall Journal: Hum Mol Genet Date: 2009-07-14 Impact factor: 6.150