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.

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-gamma coactivator-1 gene (PPARGC1A) Gly482Ser, PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -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%, chi(2 )=( )5.54 P = 0.019), whereas carriers of the PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -681C/G variants were distributed similarly among both groups. The interaction between the PPARGC1A Gly482Ser and PPAR-delta-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-gamma2 Pro12Ala variant. Although the individual studies did not reveal any statistically significant association, meta-analysis uncovered that carrying the PPAR-gamma2 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-delta and PPAR-gamma2 loci are associated with PCOS.