Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
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, 117-120Download Item:
ukmss-33681.pdf (Published (author's copy) - Peer Reviewed) 469.5Kb
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
Sponsor
Grant Number
Medical Research Council (MRC)
G0601261
Wellcome Trust
085475/Z/08/Z
Wellcome Trust
085475/B/08/Z
Wellcome Trust
084726/Z/08/Z
National Institutes of Health (NIH)
Author's Homepage:
http://people.tcd.ie/acorvinDescription:
PUBLISHEDPubMed ID: 21186350
Author: CORVIN, AIDEN PETER
Type of material:
Journal ArticleCollections:
Series/Report no:
Nature Genetics43
2
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Full text availableKeywords:
glycaemic responsLicences: