Short Communication


, Volume 49, Issue 3, pp 501-505

First online:

Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes

  • I. BarrosoAffiliated withThe Wellcome Trust Sanger Institute, Metabolic Disease Group Email author 
  • , J. LuanAffiliated withMRC Epidemiology Unit
  • , M. S. SandhuAffiliated withDepartment of Public Health & Primary Care, Institute of Public Health, University of Cambridge
  • , P. W. FranksAffiliated withMRC Epidemiology UnitPhoenix Epidemiology & Clinical Research Branch, NIDDK, NIH
  • , V. CrowleyAffiliated withDepartments of Clinical Biochemistry and Medicine, Addenbrooke’s Hospital
  • , A. J. SchaferAffiliated withIncyte Genomics
  • , S. O’RahillyAffiliated withDepartments of Clinical Biochemistry and Medicine, Addenbrooke’s Hospital
  • , N. J. WarehamAffiliated withMRC Epidemiology Unit



Peroxisome proliferator-activated receptor-γ co-activator-1α (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.

Materials and 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.


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.


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.


Association study Meta-analysis Polymorphism PPARGC1A Type 2 diabetes