The role of genetic variation in peroxisome proliferator-activated receptors in the polycystic ovary syndrome (PCOS): An original case-control study followed by systematic review and meta-analysis of existing evidence

Abstract

Objective To study the association of polymorphisms in the genes encoding peroxisome proliferator-activated receptors (PPARs) with the polycystic ovary syndrome (PCOS). Design Case-control study and meta-analysis of published evidence. Patients One hundred and sixty-one polycystic ovary syndrome patients and 113 non-hyperandrogenic women. Measurements Genotyping for PPAR-γ coactivator-1 gene (PPARGC1A) Gly482Ser, PPAR-α Leu162Val, PPAR-δ rs2267668A/G, PPAR-δ -87T/C, PPAR-γ2 Pro12Ala and PPAR-γ2 -681C/G variants and systematic review of the literature using the Entrez-PubMed search engine, followed by meta-analysis whenever possible. Results Polycystic ovary syndrome patients carried the Gly482Ser variant in PPARGC1A more frequently than controls (72% vs. 58%, χ2=5·54 P = 0·019), whereas carriers of the PPAR-α Leu162Val, PPAR-δ rs2267668A/G, PPAR-δ -87T/C, PPAR-γ2 Pro12Ala and PPAR-γ2 -681C/G variants were distributed similarly among both groups. The interaction between the PPARGC1A Gly482Ser and PPAR-δ -87T/C variants was also associated with PCOS (OR = 1·24, 95% CI 1·05-1·50, P = 0·008). The systematic review identified 31 studies addressing associations between PPARs variants and PCOS; meta-analysis was possible for nine studies focusing on the PPAR-γ2 Pro12Ala variant. Although the individual studies did not reveal any statistically significant association, meta-analysis uncovered that carrying the PPAR-γ2 Pro12Ala variant was associated with a reduced probability of having PCOS (OR = 0·77, 95% CI 0·61-0·96, P = 0·025), and that this association may be mediated by an effect on insulin sensitivity. Conclusions Common polymorphisms in the PPARGC1A, PPAR-δ and PPAR-γ2 loci are associated with PCOS. © 2010 Blackwell Publishing Ltd.