OBJECTIVE: The transcription factor 7-like 2 (TCF7L2) gene was initially reported to be associated with type 2 diabetes in Icelandic, Danish, and U.S. populations. We investigated whether TCF7L2 also has a role in type 2 diabetes susceptibility in Pima Indians. RESEARCH DESIGN AND METHODS: The six variants reported to be associated with type 2 diabetes in the Icelandic study were genotyped in a population-based sample of 3,501 Pima Indians (1,561 subjects had type 2 diabetes, and 1,940 did not have diabetes). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The one variant identified by sequencing, 35 additional database variants positioned in introns, and the six variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pima Indians. Fourteen representative variants were selected and genotyped in 3,501 Pima Indians. RESULTS: The six variants initially reported to be associated with type 2 diabetes were less common in Pima Indians compared with samples of European origin, and none were associated with type 2 diabetes. One representative variant, rs1225404, was nominally associated with type 2 diabetes in a general model (additive P = 0.03, dominant P = 0.005) but not in a within-family analysis (additive P = 0.2, dominant P = 0.07). However, several variants were associated with BMI; in particular, rs12255372 was associated in both general and within-family analyses (both P = 0.0007). Modest associations were also found with traits predictive for type 2 diabetes. CONCLUSIONS: Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population.
OBJECTIVE: The transcription factor 7-like 2 (TCF7L2) gene was initially reported to be associated with type 2 diabetes in Icelandic, Danish, and U.S. populations. We investigated whether TCF7L2 also has a role in type 2 diabetes susceptibility in Pima Indians. RESEARCH DESIGN AND METHODS: The six variants reported to be associated with type 2 diabetes in the Icelandic study were genotyped in a population-based sample of 3,501 Pima Indians (1,561 subjects had type 2 diabetes, and 1,940 did not have diabetes). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The one variant identified by sequencing, 35 additional database variants positioned in introns, and the six variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pima Indians. Fourteen representative variants were selected and genotyped in 3,501 Pima Indians. RESULTS: The six variants initially reported to be associated with type 2 diabetes were less common in Pima Indians compared with samples of European origin, and none were associated with type 2 diabetes. One representative variant, rs1225404, was nominally associated with type 2 diabetes in a general model (additive P = 0.03, dominant P = 0.005) but not in a within-family analysis (additive P = 0.2, dominant P = 0.07). However, several variants were associated with BMI; in particular, rs12255372 was associated in both general and within-family analyses (both P = 0.0007). Modest associations were also found with traits predictive for type 2 diabetes. CONCLUSIONS: Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population.
Authors: N Franceschini; K Haack; H H H Göring; V S Voruganti; S Laston; L Almasy; E T Lee; L G Best; R R Fabsitz; K E North; J W Maccluer; J B Meigs; J S Pankow; S A Cole Journal: Diabetologia Date: 2013-07-14 Impact factor: 10.122
Authors: George Stratigopoulos; Charles A LeDuc; Naoki Matsuoka; Roee Gutman; Richard Rausch; Scott A Robertson; Martin G Myers; Wendy K Chung; Streamson C Chua; Rudolph L Leibel Journal: Obesity (Silver Spring) Date: 2008-11-06 Impact factor: 5.002
Authors: Yandiswa Y Yako; Jabulisile H Madubedube; Andre P Kengne; Rajiv T Erasmus; Tahir S Pillay; Tandi E Matsha Journal: Afr Health Sci Date: 2015-12 Impact factor: 0.927
Authors: Richa Saxena; Clara C Elbers; Yiran Guo; Inga Peter; Tom R Gaunt; Jessica L Mega; Matthew B Lanktree; Archana Tare; Berta Almoguera Castillo; Yun R Li; Toby Johnson; Marcel Bruinenberg; Diane Gilbert-Diamond; Ramakrishnan Rajagopalan; Benjamin F Voight; Ashok Balasubramanyam; John Barnard; Florianne Bauer; Jens Baumert; Tushar Bhangale; Bernhard O Böhm; Peter S Braund; Paul R Burton; Hareesh R Chandrupatla; Robert Clarke; Rhonda M Cooper-DeHoff; Errol D Crook; George Davey-Smith; Ian N Day; Anthonius de Boer; Mark C H de Groot; Fotios Drenos; Jane Ferguson; Caroline S Fox; Clement E Furlong; Quince Gibson; Christian Gieger; Lisa A Gilhuijs-Pederson; Joseph T Glessner; Anuj Goel; Yan Gong; Struan F A Grant; Diederick E Grobbee; Claire Hastie; Steve E Humphries; Cecilia E Kim; Mika Kivimaki; Marcus Kleber; Christa Meisinger; Meena Kumari; Taimour Y Langaee; Debbie A Lawlor; Mingyao Li; Maximilian T Lobmeyer; Anke-Hilse Maitland-van der Zee; Matthijs F L Meijs; Cliona M Molony; David A Morrow; Gurunathan Murugesan; Solomon K Musani; Christopher P Nelson; Stephen J Newhouse; Jeffery R O'Connell; Sandosh Padmanabhan; Jutta Palmen; Sanjey R Patel; Carl J Pepine; Mary Pettinger; Thomas S Price; Suzanne Rafelt; Jane Ranchalis; Asif Rasheed; Elisabeth Rosenthal; Ingo Ruczinski; Sonia Shah; Haiqing Shen; Günther Silbernagel; Erin N Smith; Annemieke W M Spijkerman; Alice Stanton; Michael W Steffes; Barbara Thorand; Mieke Trip; Pim van der Harst; Daphne L van der A; Erik P A van Iperen; Jessica van Setten; Jana V van Vliet-Ostaptchouk; Niek Verweij; Bruce H R Wolffenbuttel; Taylor Young; M Hadi Zafarmand; Joseph M Zmuda; Michael Boehnke; David Altshuler; Mark McCarthy; W H Linda Kao; James S Pankow; Thomas P Cappola; Peter Sever; Neil Poulter; Mark Caulfield; Anna Dominiczak; Denis C Shields; Deepak L Bhatt; Deepak Bhatt; Li Zhang; Sean P Curtis; John Danesh; Juan P Casas; Yvonne T van der Schouw; N Charlotte Onland-Moret; Pieter A Doevendans; Gerald W Dorn; Martin Farrall; Garret A FitzGerald; Anders Hamsten; Robert Hegele; Aroon D Hingorani; Marten H Hofker; Gordon S Huggins; Thomas Illig; Gail P Jarvik; Julie A Johnson; Olaf H Klungel; William C Knowler; Wolfgang Koenig; Winfried März; James B Meigs; Olle Melander; Patricia B Munroe; Braxton D Mitchell; Susan J Bielinski; Daniel J Rader; Muredach P Reilly; Stephen S Rich; Jerome I Rotter; Danish Saleheen; Nilesh J Samani; Eric E Schadt; Alan R Shuldiner; Roy Silverstein; Kandice Kottke-Marchant; Philippa J Talmud; Hugh Watkins; Folkert W Asselbergs; Folkert Asselbergs; Paul I W de Bakker; Jeanne McCaffery; Cisca Wijmenga; Marc S Sabatine; James G Wilson; Alex Reiner; Donald W Bowden; Hakon Hakonarson; David S Siscovick; Brendan J Keating Journal: Am J Hum Genet Date: 2012-02-09 Impact factor: 11.025