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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)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter no keywords
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 43, Heft: 2, Seiten: 117-120 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Molecular Epidemiology (AME)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)
Institute of Epidemiology (EPI)