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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
|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.|
|Appears in Collections:||Published Articles, Dept. of Cardiovascular Sciences|
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