CONTEXT: The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. DESIGN, SETTINGS AND PARTICIPANTS: We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. MAIN OUTCOME MEASURES: Body mass index (BMI), indices of insulin sensitivity and beta-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. RESULTS: Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. CONCLUSIONS: We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.
CONTEXT: The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. DESIGN, SETTINGS AND PARTICIPANTS: We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. MAIN OUTCOME MEASURES: Body mass index (BMI), indices of insulin sensitivity and beta-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. RESULTS: Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99-2.11) and G/C: OR=1.37 (1.04-1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. CONCLUSIONS: We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.
Authors: Hemant Kulkarni; Mark Z Kos; Jennifer Neary; Thomas D Dyer; Jack W Kent; Harald H H Göring; Shelley A Cole; Anthony G Comuzzie; Laura Almasy; Michael C Mahaney; Joanne E Curran; John Blangero; Melanie A Carless Journal: Hum Mol Genet Date: 2015-06-22 Impact factor: 6.150
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
Authors: Jonathan C Schisler; Peter C Charles; Joel S Parker; Eleanor G Hilliard; Sabeen Mapara; Dane Meredith; Robert E Lineberger; Samuel S Wu; Brian D Alder; George A Stouffer; Cam Patterson Journal: PLoS One Date: 2009-12-09 Impact factor: 3.240