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

GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; Wellcome Trust Case Control Consortium 2; Zhou, Kaixin; Bellenguez, Celine; Spencer, Chris CA; Bennett, Amanda J; Coleman, Ruth L; Tavendale, Roger; Hawley, Simon A; Donnelly, Louise A; +43 more...Schofield, Chris; Groves, Christopher J; Burch, Lindsay; Carr, Fiona; Strange, Amy; Freeman, Colin; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Craddock, Nicholas; Deloukas, Panos; Dronov, Serge; Duncanson, Audrey; Edkins, Sarah; Gray, Emma; Hunt, Sarah; Jankowski, Janusz; Langford, Cordelia; Markus, Hugh S; Mathew, Christopher G; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Samani, Nilesh J; Trembath, Richard; Viswanathan, Ananth C; Wood, Nicholas W; MAGIC investigators; Harries, Lorna W; Hattersley, Andrew T; Doney, Alex SF; Colhoun, Helen; Morris, Andrew D; Sutherland, Calum; Hardie, D Grahame; Peltonen, Leena; McCarthy, Mark I; Holman, Rury R; Palmer, Colin NA; Donnelly, Peter; and Pearson, Ewan R (2011) Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nature genetics, 43 (2). pp. 117-120. ISSN 1061-4036 DOI: 10.1038/ng.735
Copy

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.
Item Type Article
Keywords ACTIVATED PROTEIN-KINASE, GENOME-WIDE ASSOCIATION, ATAXIA-TELANGIECTASIA, CANCER, CELLS, RISK, AMPK, IDENTIFICATION, HOMEOSTASIS, REDUCTASE
ISI 286623800008
Date Deposited 17 Oct 2011 13:23

Explore Further

picture_as_pdf
NIHMS33681-supplement-1.pdf
subject
Published Version
Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 3.0
View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads