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Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We carried out a GWA study on glycaemic response to metformin in 1024 Scottish patients with type 2 diabetes. Replication was in two cohorts consisting of 1783 Scottish patients and 1113 patients from the UK Prospective...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Texto |
| Lenguaje: | English |
| Publicado: |
2010
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030919/ https://www.ncbi.nlm.nih.gov/pubmed/21186350 http://dx.doi.org/10.1038/ng.735 |
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| author | Zhou, Kaixin Bellenguez, Celine Spencer, Chris CA Bennett, Amanda J Coleman, Ruth L Tavendale, Roger Hawley, Simon A. Donnelly, Louise A Schofield, Chris Groves, Christopher J Burch, Lindsay Carr, Fiona Strange, Amy Freeman, Colin Blackwell, Jenefer M Bramon, Elvira Brown, Matthew A Casas, Juan P Corvin, Aiden Craddock, Nicholas Deloukas, Panos Dronov, Serge Duncanson, Audrey Edkins, Sarah Gray, Emma Hunt, Sarah Jankowski, Janusz Langford, Cordelia Markus, Hugh S Mathew, Christopher G Plomin, Robert Rautanen, Anna Sawcer, Stephen J Samani, Nilesh J Trembath, Richard Viswanathan, Ananth C Wood, Nicholas W Harries, Lorna W Hattersley, Andrew T Doney, Alex SF Colhoun, Helen Morris, Andrew D Sutherland, Calum Hardie, D. Grahame Peltonen, Leena McCarthy, Mark I Holman, Rury R. Palmer, Colin N.A. Donnelly, Peter Pearson, Ewan R |
| author_facet | Zhou, Kaixin Bellenguez, Celine Spencer, Chris CA Bennett, Amanda J Coleman, Ruth L Tavendale, Roger Hawley, Simon A. Donnelly, Louise A Schofield, Chris Groves, Christopher J Burch, Lindsay Carr, Fiona Strange, Amy Freeman, Colin Blackwell, Jenefer M Bramon, Elvira Brown, Matthew A Casas, Juan P Corvin, Aiden Craddock, Nicholas Deloukas, Panos Dronov, Serge Duncanson, Audrey Edkins, Sarah Gray, Emma Hunt, Sarah Jankowski, Janusz Langford, Cordelia Markus, Hugh S Mathew, Christopher G Plomin, Robert Rautanen, Anna Sawcer, Stephen J Samani, Nilesh J Trembath, Richard Viswanathan, Ananth C Wood, Nicholas W Harries, Lorna W Hattersley, Andrew T Doney, Alex SF Colhoun, Helen Morris, Andrew D Sutherland, Calum Hardie, D. Grahame Peltonen, Leena McCarthy, Mark I Holman, Rury R. Palmer, Colin N.A. Donnelly, Peter Pearson, Ewan R |
| author_sort | Zhou, Kaixin |
| collection | PubMed |
| description | Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We carried out a GWA study on glycaemic response to metformin in 1024 Scottish patients with type 2 diabetes. Replication was in two cohorts consisting of 1783 Scottish patients and 1113 patients from the UK Prospective Diabetes Study. In a meta-analysis (n=3920) we observed an association (P=2.9 *10(−9)) for a SNP rs11212617 at a locus containing the ataxia telangiectasia mutated (ATM) gene with an odds ratio of 1.35 (95% CI 1.22 to 1.49) for treatment success. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMPK 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 AMPK, and variation in this gene alters glycaemic response to metformin. |
| format | Text |
| id | pubmed-3030919 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2010 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-30309192011-08-01 Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes Zhou, Kaixin Bellenguez, Celine Spencer, Chris CA Bennett, Amanda J Coleman, Ruth L Tavendale, Roger Hawley, Simon A. Donnelly, Louise A Schofield, Chris Groves, Christopher J Burch, Lindsay Carr, Fiona Strange, Amy Freeman, Colin Blackwell, Jenefer M Bramon, Elvira Brown, Matthew A Casas, Juan P Corvin, Aiden Craddock, Nicholas Deloukas, Panos Dronov, Serge Duncanson, Audrey Edkins, Sarah Gray, Emma Hunt, Sarah Jankowski, Janusz Langford, Cordelia Markus, Hugh S Mathew, Christopher G Plomin, Robert Rautanen, Anna Sawcer, Stephen J Samani, Nilesh J Trembath, Richard Viswanathan, Ananth C Wood, Nicholas W Harries, Lorna W Hattersley, Andrew T Doney, Alex SF Colhoun, Helen Morris, Andrew D Sutherland, Calum Hardie, D. Grahame Peltonen, Leena McCarthy, Mark I Holman, Rury R. Palmer, Colin N.A. Donnelly, Peter Pearson, Ewan R Nat Genet Article Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We carried out a GWA study on glycaemic response to metformin in 1024 Scottish patients with type 2 diabetes. Replication was in two cohorts consisting of 1783 Scottish patients and 1113 patients from the UK Prospective Diabetes Study. In a meta-analysis (n=3920) we observed an association (P=2.9 *10(−9)) for a SNP rs11212617 at a locus containing the ataxia telangiectasia mutated (ATM) gene with an odds ratio of 1.35 (95% CI 1.22 to 1.49) for treatment success. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMPK 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 AMPK, and variation in this gene alters glycaemic response to metformin. 2010-12-26 2011-02 /pmc/articles/PMC3030919/ /pubmed/21186350 http://dx.doi.org/10.1038/ng.735 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Zhou, Kaixin Bellenguez, Celine Spencer, Chris CA Bennett, Amanda J Coleman, Ruth L Tavendale, Roger Hawley, Simon A. Donnelly, Louise A Schofield, Chris Groves, Christopher J Burch, Lindsay Carr, Fiona Strange, Amy Freeman, Colin Blackwell, Jenefer M Bramon, Elvira Brown, Matthew A Casas, Juan P Corvin, Aiden Craddock, Nicholas Deloukas, Panos Dronov, Serge Duncanson, Audrey Edkins, Sarah Gray, Emma Hunt, Sarah Jankowski, Janusz Langford, Cordelia Markus, Hugh S Mathew, Christopher G Plomin, Robert Rautanen, Anna Sawcer, Stephen J Samani, Nilesh J Trembath, Richard Viswanathan, Ananth C Wood, Nicholas W Harries, Lorna W Hattersley, Andrew T Doney, Alex SF Colhoun, Helen Morris, Andrew D Sutherland, Calum Hardie, D. Grahame Peltonen, Leena McCarthy, Mark I Holman, Rury R. Palmer, Colin N.A. Donnelly, Peter Pearson, Ewan R Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title_full | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title_fullStr | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title_full_unstemmed | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title_short | Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes |
| title_sort | common variants near atm are associated with glycemic response to metformin in type 2 diabetes |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030919/ https://www.ncbi.nlm.nih.gov/pubmed/21186350 http://dx.doi.org/10.1038/ng.735 |
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