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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
Author(s) -
SanMillán José L.,
EscobarMorreale Héctor F.
Publication year - 2010
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2009.03679.x
Subject(s) - polycystic ovary , medicine , endocrinology , coactivator , peroxisome proliferator activated receptor , ppargc1a , meta analysis , biology , insulin resistance , bioinformatics , receptor , obesity , genetics , gene , transcription factor
Summary 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%, χ 2 = 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.