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

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The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group, The Wellcome Trust Case Control Consortium 2·2011·Nature Genetics

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.

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Metadata

Authors
The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group, & The Wellcome Trust Case Control Consortium 2
Venue
Nature Genetics
Published
2010-12-26
Volume
43
Issue
2
Pages
117-120
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2162897961
Cited by
432
References
38
FWCI
15.01
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. https://app.cochat.ai/papers/10.1038/ng.735
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The GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group, & The Wellcome Trust Case Control Consortium 2. (2011). Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nature Genetics. https://doi.org/10.1038/ng.735

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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