Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes.
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.
Barroso
I
I
The Wellcome Trust Sanger Institute, Metabolic Disease Group, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. ib1@sanger.ac.uk
Luan
J
J
Sandhu
M S
MS
Franks
P W
PW
Crowley
V
V
Schafer
A J
AJ
O'Rahilly
S
S
Wareham
N J
NJ
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*
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