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, Tavendale, Roger, Donnelly, Louise A., Schofield, Chris, Burch, Lindsay, Carr, Fiona, Colhoun, Helen, Morris, Andrew D., Sutherland, Calum, Palmer, Colin N. A., Pearson, Ewan, Bellenguez Celine, Spencer, Chris C. A., Strange, Amy, Freeman, Colin, Rautanen, Anna, McCarthy, Mark I., Donnelly, Peter, Bennett, Amanda J., Coleman, Ruth L., Groves, Christopher J., McCarthy, Mark I., Holman, Rury R., Hawley, Simon A., Hardie, Grahame, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Craddock, Nicholas, Deloukas, Panos, Dronov, Serge, Edkins, Sarah, Gray, Emma, Hunt, Sarah, Langford, Cordelia, Peltonen, Leena, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G, Trembath, Richard, Plomin, Robert, Sawcer, Stephen J., Samani, Nilesh J., Viswanathan, Aananth C., Wood, Nicholas W., Harries, Lorna W., Hattersley, Andrew T., Doney, Alex S. F., McCarthy, Mark I. and Donnelly, Peter (2011) Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nature Genetics, 43 2: 117-120. doi:10.1038/ng.735

Author GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group
Wellcome Trust Case Control Consortium 2
Zhou, Kaixin
Tavendale, Roger
Donnelly, Louise A.
Schofield, Chris
Burch, Lindsay
Carr, Fiona
Colhoun, Helen
Morris, Andrew D.
Sutherland, Calum
Palmer, Colin N. A.
Pearson, Ewan
Bellenguez Celine
Spencer, Chris C. A.
Strange, Amy
Freeman, Colin
Rautanen, Anna
McCarthy, Mark I.
Donnelly, Peter
Bennett, Amanda J.
Coleman, Ruth L.
Groves, Christopher J.
McCarthy, Mark I.
Holman, Rury R.
Hawley, Simon A.
Hardie, Grahame
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Craddock, Nicholas
Deloukas, Panos
Dronov, Serge
Edkins, Sarah
Gray, Emma
Hunt, Sarah
Langford, Cordelia
Peltonen, Leena
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S.
Mathew, Christopher G
Trembath, Richard
Plomin, Robert
Sawcer, Stephen J.
Samani, Nilesh J.
Viswanathan, Aananth C.
Wood, Nicholas W.
Harries, Lorna W.
Hattersley, Andrew T.
Doney, Alex S. F.
McCarthy, Mark I.
Donnelly, Peter
Title Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Formatted title
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2011-02
Year available 2010
Sub-type Article (original research)
DOI 10.1038/ng.735
Volume 43
Issue 2
Start page 117
End page 120
Total pages 4
Place of publication New York, NY, U.S.A.
Publisher Nature Publishing Group
Collection year 2011
Language eng
Formatted abstract
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.
© 2011 Nature America, Inc. All rights reserved.
Keyword Activated Protein-kinase
Genome-wide association
Ataxia telangiectasia
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published online 26 December 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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UQ Diamantina Institute Publications
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Created: Fri, 25 Feb 2011, 10:50:46 EST by Kylie Hengst on behalf of UQ Diamantina Institute