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).


METHODS
Case-control study and meta-analysis of published evidence.


METHODS
One hundred and sixty-one polycystic ovary syndrome patients and 113 non-hyperandrogenic women.


METHODS
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.
San-Millán
José L
JL
Department of Molecular Genetics, Hospital Universitario Ramon y Cajal & Universidad de Alcala, Madrid, Spain.
Escobar-Morreale
Héctor F
HF
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D013030:Spain; D055815:Young Adult
D047492:Peroxisome Proliferator-Activated Receptors