title: Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PPARGC1A) is a transcriptional co-activator with a central role in energy expenditure and glucose metabolism. Several studies have suggested that the common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2 diabetes, with conflicting results. To clarify the role of Gly482Ser in type 2 diabetes and related human metabolic phenotypes we genotyped this polymorphism in a case-control study and performed a meta-analysis of relevant published data.
  
  
  METHODS
  Gly482Ser was genotyped in a type 2 diabetes case-control study (N=1,096) using MassArray technology. A literature search revealed publications that examined Gly482Ser for association with type 2 diabetes and related metabolic phenotypes. Meta-analysis of the current study and relevant published data was undertaken.
  
  
  RESULTS
  In the pooled meta-analysis, including data from this study and seven published reports (3,718 cases, 4,818 controls), there was evidence of between-study heterogeneity (p<0.1). In the fixed-effects meta-analysis, the pooled odds ratio for risk of type 2 diabetes per Ser482 allele was 1.07 (95% CI 1.00-1.15, p=0.044). Elimination of one of the studies from the meta-analysis gave a summary odds ratio of 1.11 (95% CI 1.04-1.20, p=0.004), with no between-study heterogeneity (p=0.475). For quantitative metabolic traits in normoglycaemic subjects, we also found significant between-study heterogeneity. However, no significant association was observed between Gly482Ser and BMI, fasting glucose or fasting insulin.
  
  
  CONCLUSIONS
  This meta-analysis of data from the current and published studies supports a modest role for the Gly482Ser PPARGC1A variant in type 2 diabetes risk.
authors.affiliation: The Wellcome Trust Sanger Institute, Metabolic Disease Group, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. ib1@sanger.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Barroso
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: M S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: P W
authors.initials: PW
authors.lastname: Franks
authors.forename: V
authors.initials: V
authors.lastname: Crowley
authors.forename: A J
authors.initials: AJ
authors.lastname: Schafer
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005215:Fasting; D005998:Glycine / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012694:Serine / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D006360:Heat-Shock Proteins; D007328:Insulin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D012694:Serine; D005998:Glycine