The C allele of ATM rs11212617 does not associate with metformin response in the diabetes prevention program
Volume 35, Issue 9
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
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.
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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