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Title: Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes.
Authors: GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group
Wellcome Trust Case Control Consortium 2
Zhou, K
Bellenguez, C
Spencer, CC
Bennett, AJ
Coleman, RL
Tavendale, R
Hawley, SA
Donnelly, LA
Schofield, C
Groves, CJ
Burch, L
Carr, F
Strange, A
Freeman, C
Blackwell, JM
Bramon, E
Brown, MA
Casas, JP
Corvin, A
Craddock, N
Deloukas, P
Dronov, S
Duncanson, A
Edkins, S
Gray, E
Hunt, S
Jankowski, J
Langford, C
Markus, HS
Mathew, CG
Plomin, R
Rautanen, A
Sawcer, SJ
Samani, NJ
Trembath, R
Viswanathan, AC
Wood, NW
MAGIC, investigators
Harries, LW
Hattersley, AT
Doney, AS
Colhoun, H
Morris, AD
Sutherland, C
Hardie, DG
Peltonen, L
McCarthy, MI
Holman, RR
Palmer, CN
Donnelly, P
Pearson, ER
First Published: Feb-2011
Citation: NAT GENET, 2011, 43 (2), pp. 117-120
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.
DOI Link: 10.1038/ng.735
eISSN: 1546-1718
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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