The C allele of ATM rs11212617 does not associate with metformin response in the diabetes prevention program

Authors

Jose C. Florez, Massachusetts General Hospital, Boston, MA
Kathleen A. Jablonski, George Washington UniversityFollow
Andrew Taylor, Massachusetts General Hospital, Boston, MA
Kieren Mather, Indiana UniversityFollow
Edward Horton, Harvard Medical SchoolFollow
Neil H. White, Washington University in St LouisFollow
Elizabeth Barrett-Connor, University of California, San Diego
William C. Knowler, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
Alan R. Shuldiner, University of Maryland
Toni I. Pollin, University of Maryland

Document Type

Journal Article

Publication Date

9-2012

Journal

Diabetes Care

Volume

Volume 35, Issue 9

Inclusive Pages

1864-1867

Keywords

Cell Cycle Proteins--genetics; DNA-Binding Proteins--genetics; Diabetes Mellitus--blood; Diabetes Mellitus--genetics; Diabetes Mellitus--metabolism; Diabetes Mellitus--prevention & control; Hypoglycemic Agents--therapeutic use; Metformin--therapeutic use; Polymorphism; Genetic--genetics; Protein-Serine-Threonine Kinases--genetics; Tumor Suppressor Proteins--genetics

Abstract

OBJECTIVE The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia–mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes. We tested whether this variant modified the effect of metformin in the Diabetes Prevention Program (DPP), in which metformin reduced diabetes incidence by 31% in volunteers with impaired glucose tolerance.

RESEARCH DESIGN AND METHODS We genotyped rs11212617 in 2,994 DPP participants and analyzed its effects on diabetes incidence and related traits.

RESULTS Contrary to expectations, C carriers enjoyed no preventive advantage on metformin; their hazard ratio, compared with A carriers, was 1.17 ([95% CI 0.96–1.42], P= 0.13) under metformin. There were no significant differences by genotype in metformin’s effects on insulin sensitivity, fasting glucose, glycated hemoglobin, or disposition index.

CONCLUSIONS The reported association of rs11212617 with metformin response was not confirmed for diabetes prevention or for effects on relevant physiologic parameters in the DPP.

Comments

Reproduced with permission of the American Diabetes Association. Diabetes Care.

This is an open access PubMed Central article. Click on link for full-text access.

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

APA Citation

Florez, J. C., Barrett-Connor, E., Jablonski, K. A., Knowler, W. C., Taylor, A., Shuldiner, A. R., Mather, K., Pollin, T.I., Horton, E., White, N. H. (2012). The C allele of ATM rs11212617 does not associate with metformin response in the diabetes prevention program. Diabetes Care, 35(9), 1864-1867

Peer Reviewed

1

Open Access

1