A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
作者： Valgerdur Steinthorsdottir , Gudmar Thorleifsson , Inga Reynisdottir , Rafn Benediktsson , Thorbjorg Jonsdottir
DOI: 10.1038/NG2043
关键词:
摘要: We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, we found that previously described variant the transcription factor 7-like gene (TCF7L2) conferred most significant risk. In addition to confirming two recently identified risk variants, CDKAL1 was associated with T2D individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P 7.7 x 10(-9)) from Hong Kong Han Chinese (OR 1.25 (1.11-1.40), 0.00018). The genotype OR this suggested effect substantially stronger homozygous carriers than heterozygous carriers. ORs homozygotes were 1.50 (1.31-1.72) 1.55 (1.23-1.95) groups, respectively. insulin response approximately 20% lower heterozygotes or noncarriers, suggesting confers through reduced secretion.
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Charles N Rotimi, Georgia M Dunston, Kate Berg, Omobosola Akinsete, Albert Amoah, Samuel Owusu, Joseph Acheampong, Kofi Boateng, Johnnie Oli, Godfrey Okafor, Belonwu Onyenekwe, Babatunde Osotimehin, Fayeofori Abbiyesuku, Thomas Johnson, Olufemi Fasanmade, Paulette Furbert-Harris, Rick Kittles, Mirjana Vekich, Olufemi Adegoke, George Bonney, Francis Collins, None, In Search of Susceptibility Genes for Type 2 Diabetes in West Africa: The Design and Results of the First Phase of the AADM Study Annals of Epidemiology. ,vol. 11, pp. 51- 58 ,(2001) , 10.1016/S1047-2797(00)00180-0
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, Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes Nature Genetics. ,vol. 38, pp. 320- 323 ,(2006) , 10.1038/NG1732
F. Chimienti, S. Devergnas, A. Favier, M. Seve, Identification and Cloning of a β-Cell–Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules Diabetes. ,vol. 53, pp. 2330- 2337 ,(2004) , 10.2337/DIABETES.53.9.2330
Torben Jørgensen, Knut Borch-Johnsen, Troels F. Thomsen, Hans Ibsen, Charlotte Glümer, Charlotta Pisinger, A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99 (1) European Journal of Preventive Cardiology. ,vol. 10, pp. 377- 386 ,(2003) , 10.1097/01.HJR.0000096541.30533.82
Mariano Ubeda, J. Michael Rukstalis, Joel F. Habener, Inhibition of Cyclin-dependent Kinase 5 Activity Protects Pancreatic Beta Cells from Glucotoxicity Journal of Biological Chemistry. ,vol. 281, pp. 28858- 28864 ,(2006) , 10.1074/JBC.M604690200
B. Devlin, Kathryn Roeder, Genomic control for association studies. Biometrics. ,vol. 55, pp. 997- 1004 ,(1999) , 10.1111/J.0006-341X.1999.00997.X
Fan-Yan Wei, Kazuaki Nagashima, Toshio Ohshima, Yasunori Saheki, Yun-Fei Lu, Masayuki Matsushita, Yuichiro Yamada, Katsuhiko Mikoshiba, Yutaka Seino, Hideki Matsui, Kazuhito Tomizawa, Cdk5-dependent regulation of glucose-stimulated insulin secretion Nature Medicine. ,vol. 11, pp. 1104- 1108 ,(2005) , 10.1038/NM1299
Yick-Pang Ching, Andy S. H. Pang, Wing-Ho Lam, Robert Z. Qi, Jerry H. Wang, Identification of a neuronal Cdk5 activator-binding protein as Cdk5 inhibitor. Journal of Biological Chemistry. ,vol. 277, pp. 15237- 15240 ,(2002) , 10.1074/JBC.C200032200
X. Yang, W.-Y. So, A. P.S. Kong, C.-S. Ho, C. W.K. Lam, R. J. Stevens, R. R. Lyu, D. D. Yin, C. S. Cockram, P. C.Y. Tong, V. Wong, J. C.N. Chan, Development and validation of stroke risk equation for Hong Kong Chinese patients with type 2 diabetes: the Hong Kong Diabetes Registry. Diabetes Care. ,vol. 30, pp. 65- 70 ,(2007) , 10.2337/DC06-1273
Robert Sladek, Ghislain Rocheleau, Johan Rung, Christian Dina, Lishuang Shen, David Serre, Philippe Boutin, Daniel Vincent, Alexandre Belisle, Samy Hadjadj, Beverley Balkau, Barbara Heude, Guillaume Charpentier, Thomas J. Hudson, Alexandre Montpetit, Alexey V. Pshezhetsky, Marc Prentki, Barry I. Posner, David J. Balding, David Meyre, Constantin Polychronakos, Philippe Froguel, A genome-wide association study identifies novel risk loci for type 2 diabetes Nature. ,vol. 445, pp. 881- 885 ,(2007) , 10.1038/NATURE05616