| dc.contributor.author | CORVIN, AIDEN PETER | en |
| dc.date.accessioned | 2013-08-07T15:40:55Z | |
| dc.date.available | 2013-08-07T15:40:55Z | |
| dc.date.issued | 2011 | en |
| dc.date.submitted | 2011 | en |
| dc.identifier.citation | Zhou, K., Bellenguez, C., Spencer, C.C.A., Bennett, A.J., Coleman, R.L., Tavendale, R., Hawley, S.A., (...), Pearson, E.R., Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes, Nature Genetics, 43, 2, 2011, 117-120 | en |
| dc.identifier.other | Y | en |
| dc.description | PUBLISHED | en |
| dc.description | PubMed ID: 21186350 | en |
| dc.description.abstract | Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We carried
out a GWA study on glycaemic response to metformin in 1024 Scottish patients with type 2
diabetes. Replication was in two cohorts consisting of 1783 Scottish patients and 1113 patients
from the UK Prospective Diabetes Study. In a meta-analysis (n=3920) we observed an association
(P=2.9 *10
?9
) for a SNP rs11212617 at a locus containing the
ataxia telangiectasia mutated
(
ATM
) gene with an odds ratio of 1.35 (95% CI 1.22 to 1.49) for treatment success. In a rat
hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and
activation of AMPK in response to metformin. We conclude that
ATM,
a gene known to beinvolved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of
AMPK, and variation in this gene alters glycaemic response to metformin | en |
| dc.description.sponsorship | We are grateful to all the participants who took part in this study, to the general practitioners, to the Scottish School
of Primary Care for their help in recruiting the participants, and to the whole team, which includes interviewers,
computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and
nurses. The Wellcome Trust provides support for Wellcome Trust United Kingdom Type 2 Diabetes Case Control
Collection (GoDARTS) and informatics support is provided by the Chief Scientist Office. The Wellcome Trust
funds the Scottish Health Informatics Programme, provides core support for the Wellcome Trust Centre for Human
Genetics in Oxford and funds the Wellcome Trust Case Control Consortium 2. This research was specifically
funded by Diabetes UK (07/0003525), MRC (G0601261) and the Wellcome Trust (084726/Z/08/Z, 085475/Z/08/Z,
085475/B/08/Z). We also acknowledge support from the NIHR award to Moorfields Eye Hospital NHS Foundation
Trust and University College London Institute of Ophthalmology for a Specialist Biomedical Research Centre for
Ophthalmology (ACV). P. Donnelly was supported in part by a Wolfson?Royal Society Merit Award. KZ holds a
Henry Wellcome Post-Doctoral Fellowship. SAH and DGH were supported by the EXGENESIS consortium
(LSHM-CT-2004-005272) funded by the European Commission | en |
| dc.format.extent | 117-120 | en |
| dc.language.iso | en | en |
| dc.relation.ispartofseries | Nature Genetics | en |
| dc.relation.ispartofseries | 43 | en |
| dc.relation.ispartofseries | 2 | en |
| dc.rights | Y | en |
| dc.subject | glycaemic respons | en |
| dc.subject.lcsh | glycaemic respons | en |
| dc.title | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes | en |
| dc.type | Journal Article | en |
| dc.type.supercollection | scholarly_publications | en |
| dc.type.supercollection | refereed_publications | en |
| dc.identifier.peoplefinderurl | http://people.tcd.ie/acorvin | en |
| dc.identifier.rssinternalid | 73741 | en |
| dc.contributor.sponsor | Medical Research Council (MRC) | en |
| dc.contributor.sponsorGrantNumber | G0601261 | en |
| dc.contributor.sponsor | Wellcome Trust | en |
| dc.contributor.sponsorGrantNumber | 085475/Z/08/Z | en |
| dc.contributor.sponsor | Wellcome Trust | en |
| dc.contributor.sponsorGrantNumber | 085475/B/08/Z | en |
| dc.contributor.sponsor | Wellcome Trust | en |
| dc.contributor.sponsorGrantNumber | 084726/Z/08/Z | en |
| dc.contributor.sponsor | National Institutes of Health (NIH) | en |
| dc.identifier.uri | http://hdl.handle.net/2262/66912 | |
