The C Allele of ATM Rs11212617 Does Not Associate with Metformin Response in the Diabetes Prevention Program

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2012 Jul 4

PMID 22751958

Citations 37

Authors

Jose C Florez

Kathleen A Jablonski

Andrew Taylor

Kieren Mather

Edward Horton

Neil H White

Elizabeth Barrett-Connor

William C Knowler

Alan R Shuldiner

Toni I Pollin

Affiliations

Soon will be listed here.

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.

Citing Articles

Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP).

Li J, Perry J, Jablonski K, Srinivasan S, Chen L, Todd J Diabetes. 2022; 72(8):1161-1172.

PMID: 36525397 PMC: 10382652. DOI: 10.2337/db22-0702.

On the Verge of Precision Medicine in Diabetes.

Li J, Florez J Drugs. 2022; 82(13):1389-1401.

PMID: 36123514 PMC: 9531144. DOI: 10.1007/s40265-022-01774-4.

Genetic and Phenotypic Factors Affecting Glycemic Response to Metformin Therapy in Patients with Type 2 Diabetes Mellitus.

Nasykhova Y, Barbitoff Y, Tonyan Z, Danilova M, Nevzorov I, Komandresova T Genes (Basel). 2022; 13(8).

PMID: 35893047 PMC: 9330240. DOI: 10.3390/genes13081310.

Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes.

Kawoosa F, Shah Z, Masoodi S, Amin A, Rasool R, Fazili K BMC Endocr Disord. 2022; 22(1):140.

PMID: 35619086 PMC: 9137212. DOI: 10.1186/s12902-022-01033-3.

A Two-Stage Study Identifies Two Novel Polymorphisms in Affecting Metformin Response in Chinese Type 2 Diabetes Patients.

Xiao D, Liu J, Zhang S, Liu R, Yin J, Han X Pharmgenomics Pers Med. 2021; 14:745-755.

PMID: 34188521 PMC: 8236263. DOI: 10.2147/PGPM.S305020.

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