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GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group (Zhou, K.* ; Bellenguez, C.* ; Spencer, C.C.* ; Bennett, A.J.* ; Coleman, R.L.* ; Tavendale, R.* ; Hawley, S.A.* ; Donnelly, L.A.* ; Schofield, C.* ; Groves, C.J.* ; Burch, L.* ; Carr, F.* ; Strange, A.* ; Freeman, C.* ; Blackwell, J.M.* ; Bramon, E.* ; Brown, M.A.* ; Casas, J.P.* ; Corvin, A.* ; Craddock, N.* ; Deloukas, P.* ; Dronov, S.* ; Duncanson, A.* ; Edkins, S.* ; Gray, E.* ; Hunt, S.* ; Jankowski, J.* ; Langford, C.* ; Markus, H.S.* ; Mathew, C.G.* ; Plomin, R.* ; Rautanen, A.* ; Sawcer, S.J.* ; Samani, N.J.* ; Trembath, R.* ; Viswanathan, A.C.* ; Wood, N.W* ; Harries, L.W.* ; Hattersley, A.T.* ; Doney, A.S.* ; Colhoun, H.* ; Morris, A.D.* ; Sutherland, C.* ; Hardie, D.G.* ; Peltonen, L.* ; McCarthy, M.I.* ; Holman, R.R.* ; Palmer, C.N.* ; Donnelly, P.* ; Pearson, E.R.*) ; Wellcome Trust Case Control Consortium 2 (WTCCC2) (*) ; MAGIC Investigators (Grallert, H. ; Gieger, C. ; Meisinger, C. ; Thorand, B. ; Wichmann, H.-E. ; Illig, T.)

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.

Nat. Genet. 43, 117-120 (2011)
Open Access Green as soon as Postprint is submitted to ZB.
Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.
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Publication type Article: Journal article
Document type Scientific Article
Keywords no keywords
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 43, Issue: 2, Pages: 117-120 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed