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Nat Genet. 2011 Feb;43(2):117-20. doi: 10.1038/ng.735. Epub 2010 Dec 26.

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

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1
Biomedical Research Institute, University of Dundee, Dundee, UK.

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.

PMID:
21186350
PMCID:
PMC3030919
DOI:
10.1038/ng.735
[Indexed for MEDLINE]
Free PMC Article
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