UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

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

Zhou, KX; Bellenguez, C; Spencer, CCA; Bennett, AJ; Coleman, RL; Tavendale, R; Hawley, SA; ... MAGIC Investigators, ; + view all (2011) Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. NAT GENET , 43 (2) 117 - U57. 10.1038/ng.735.

Full text not available from this repository.

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 x 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.

Type: Article
Title: Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
DOI: 10.1038/ng.735
Keywords: ACTIVATED PROTEIN-KINASE, GENOME-WIDE ASSOCIATION, ATAXIA-TELANGIECTASIA, CANCER, CELLS, RISK, AMPK, IDENTIFICATION, HOMEOSTASIS, REDUCTASE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics
URI: http://discovery.ucl.ac.uk/id/eprint/1298554
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item