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

Kaixin Zhou; Celine Bellenguez; Chris C. A. Spencer; Amanda J. Bennett; Ruth L. Coleman; Roger Tavendale; Simon A. Hawley; Louise A. Donnelly; Chris Schofield; Christopher J. Groves; Lindsay Burch; Fiona Carr; Amy Strange; Colin Freeman; Jenefer M. Blackwell; Elvira Bramon; Matthew A. Brown; Juan P. Casas; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Serge Dronov; Audrey Duncanson; Sarah Edkins; Emma Gray; Sarah Hunt; Janusz Jankowski; Cordelia Langford; Hugh S. Markus; Christopher G. Mathew; Robert Plomin; Anna Rautanen; Stephen J. Sawcer; Nilesh J. Samani; Richard Trembath; Ananth C. Viswanathan; Nicholas W. Wood; Lorna W. Harries; Andrew T. Hattersley; Alex S. F. Doney; Helen Colhoun; Andrew D. Morris; Calum Sutherland; D. Grahame Hardie; Leena Peltonen; Mark I. McCarthy; Rury R. Holman; Colin N. A. Palmer; Peter Donnelly; Ewan R. Pearson; GoDARTS UKPDS Diabet Pharmacogenet

doi:10.1038/ng.735

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

Journal article

Peer reviewed

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

Kaixin Zhou, Celine Bellenguez, Chris C. A. Spencer, Amanda J. Bennett, Ruth L. Coleman, Roger Tavendale, Simon A. Hawley, Louise A. Donnelly, Chris Schofield, Christopher J. Groves, …

Nature genetics, Vol.43(2), pp.117-U57

01/02/2011

DOI: https://doi.org/10.1038/ng.735

PMCID: PMC3030919

PMID: 21186350

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 x 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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Title: Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Creators - without role: Kaixin Zhou - University of Dundee
Celine Bellenguez - Wellcome Centre for Human Genetics
Chris C. A. Spencer - Wellcome Trust
Amanda J. Bennett - University of Oxford
Ruth L. Coleman - University of Oxford
Roger Tavendale - University of Dundee
Simon A. Hawley - University of Dundee
Louise A. Donnelly - University of Dundee
Chris Schofield - University of Dundee
Christopher J. Groves - National Institute for Health Research
Lindsay Burch - University of Dundee
Fiona Carr - University of Dundee
Amy Strange - Wellcome Centre for Human Genetics
Colin Freeman - Wellcome Trust
Jenefer M. Blackwell - University of Western Australia
Elvira Bramon - King's College London
Matthew A. Brown - University of Queensland
Juan P. Casas - Supreme Council Of Health
Aiden Corvin - Trinity College Dublin
Nicholas Craddock - Cardiff University
Panos Deloukas - Wellcome Trust
Serge Dronov - Wellcome Trust
Audrey Duncanson - Wellcome Trust
Sarah Edkins - Wellcome Trust
Emma Gray - Wellcome Sanger Institute
Sarah Hunt - Wellcome Sanger Institute
Janusz Jankowski - Queen Mary University of London
Cordelia Langford - Wellcome Trust
Hugh S. Markus - St George's, University of London
Christopher G. Mathew - Supreme Council Of Health
Robert Plomin - King's College London
Anna Rautanen - Wellcome Centre for Human Genetics
Stephen J. Sawcer - University of Cambridge
Nilesh J. Samani - University College London
Richard Trembath - Supreme Council Of Health
Ananth C. Viswanathan - Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England
Nicholas W. Wood - University of Edinburgh
Lorna W. Harries - University of Exeter
Andrew T. Hattersley - University of Exeter
Alex S. F. Doney - University of Exeter
Helen Colhoun - Ninewells Hospital
Andrew D. Morris - University of Dundee
Calum Sutherland - University of Dundee
D. Grahame Hardie - University of Dundee
Leena Peltonen - University of Dundee
Mark I. McCarthy - University of Oxford
Rury R. Holman - University of Oxford
Colin N. A. Palmer - University of Dundee
Peter Donnelly - Wellcome Trust
Ewan R. Pearson - University of Dundee
GoDARTS UKPDS Diabet Pharmacogenet
Publication Details: Nature genetics, Vol.43(2), pp.117-U57
Publisher: Springer Nature
Number of pages: 6
Grant note: NF-SI-0507-10379; PDA/02/06/016 / National Institute for Health Research; National Institutes of Health Research (NIHR) G0601261 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 07/0003525 / Diabetes UK Henry Wellcome Post-Doctoral Fellowship; Wellcome Trust G19/2; G9817803B; G0601261; G0901310 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) National Institute for Health Research; National Institutes of Health Research (NIHR) 084726/Z/08/Z; 085475/Z/08/Z; 085475/B/08/Z / Wellcome Trust Wolfson-Royal Society Merit Award; Royal Society LSHM-CT-2004-005272 / European Commission; European Commission Joint Research Centre G19/2; G0901310; G0601261 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9936203308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article