AIMS/HYPOTHESIS: The sterol regulatory element-binding factor (SREBF)-1c is a transcription factor involved in the regulation of lipid and glucose metabolism. We have previously found evidence that a common SREBF1c single-nucleotide polymorphism (SNP), located between exons 18c and 19c, is associated with an increased risk of type 2 diabetes. The present study aimed to replicate our previously reported association in a larger case-control study and to examine an additional five SREBF1c SNPs for their association with diabetes risk and plasma glucose concentrations. METHODS: We genotyped six SREBF1c SNPs in two case-control studies (n=1,938) and in a large cohort study (n=1,721) and tested for association with type 2 diabetes and with plasma glucose concentrations (fasting and 120-min post-glucose load), respectively. RESULTS: In the case-control studies, carriers of the minor allele of the previously reported SNP (rs11868035) had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04-1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018), located in the 5' region, were significantly associated with diabetes risk (OR > or =1.21, p< or =0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the 5' region were weakly (p<0.09) associated with plasma glucose concentrations in the cohort study. Rare homozygotes had increased (p< or =0.05) 120-min post-load glucose concentrations compared with carriers of the wild-type allele. Haplotype analyses showed significant (p=0.04) association with diabetes risk and confirmed the single SNP analyses. CONCLUSIONS/ INTERPRETATION: In summary, we replicated our previous finding and found evidence for SNPs in the 5' region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration.
AIMS/HYPOTHESIS: The sterol regulatory element-binding factor (SREBF)-1c is a transcription factor involved in the regulation of lipid and glucose metabolism. We have previously found evidence that a common SREBF1c single-nucleotide polymorphism (SNP), located between exons 18c and 19c, is associated with an increased risk of type 2 diabetes. The present study aimed to replicate our previously reported association in a larger case-control study and to examine an additional five SREBF1c SNPs for their association with diabetes risk and plasma glucose concentrations. METHODS: We genotyped six SREBF1c SNPs in two case-control studies (n=1,938) and in a large cohort study (n=1,721) and tested for association with type 2 diabetes and with plasma glucose concentrations (fasting and 120-min post-glucose load), respectively. RESULTS: In the case-control studies, carriers of the minor allele of the previously reported SNP (rs11868035) had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04-1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018), located in the 5' region, were significantly associated with diabetes risk (OR > or =1.21, p< or =0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the 5' region were weakly (p<0.09) associated with plasma glucose concentrations in the cohort study. Rare homozygotes had increased (p< or =0.05) 120-min post-load glucose concentrations compared with carriers of the wild-type allele. Haplotype analyses showed significant (p=0.04) association with diabetes risk and confirmed the single SNP analyses. CONCLUSIONS/ INTERPRETATION: In summary, we replicated our previous finding and found evidence for SNPs in the 5' region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration.
Authors: D R Williams; N J Wareham; D C Brown; C D Byrne; P M Clark; B D Cox; L J Cox; N E Day; C N Hales; C R Palmer Journal: Diabet Med Date: 1995-01 Impact factor: 4.359
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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