title: The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program.
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.
  
  
  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.
authors: Massachusetts General Hospital, Boston, MA, USA. jcflorez@partners.org
authors: Jose C
authors: JC
authors: Florez
authors: Kathleen A
authors: KA
authors: Jablonski
authors: Andrew
authors: A
authors: Taylor
authors: Kieren
authors: K
authors: Mather
authors: Edward
authors: E
authors: Horton
authors: Neil H
authors: NH
authors: White
authors: Elizabeth
authors: E
authors: Barrett-Connor
authors: William C
authors: WC
authors: Knowler
authors: Alan R
authors: AR
authors: Shuldiner
authors: Toni I
authors: TI
authors: Pollin
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D001786:Blood Glucose / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D005215:Fasting / Q000097:blood; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D001786:Blood Glucose; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human