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The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome


Onno E. Janssen, Division of Endocrinology, Department of Medicine, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. Tel: +49 201723 2854; Fax: +49 201723 5976; E-mail:


Background  Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and chronic anovulation. The genetic background of the insulin resistance frequently associated with PCOS is unclear.

Objectives  To examine the influe nce of the Pro12Ala polymorphism of the peroxisome proliferator activated receptor gamma (PPARγ), which is thought to play a role in the regulation of insulin sensitivity, on endocrine and metabolic parameters in PCOS patients.

Methods  PPARγ alleles were analysed in 102 PCOS patients (age 27 ± 5·3 years) and 104 age matched control women. PCOS was defined by the NIH-criteria as the presence of chronic oligo- or anovulation and hyperandrogenism. Family history and clinical parameters were evaluated by personal interview and physical examination, parameters of insulin resistance [homeostasis model assessment (HOMA) and Matsuda-index] were evaluated with a glucose tolerance test.

Results  Seventy-nine (77·5%) PCOS patients were carriers of the wild-type PPARγ allele (Pro/Pro), while 23 (22·5%) had at least one Ala allele (X/Ala), with an equal distribution in controls. X/Ala PCOS women were more insulin-sensitive, evidenced by lower fasting insulin, HOMA index and insulin secretion. Differences in insulin resistance did not depend on body mass index. The genotype had no influence on lipid status, leptin, adiponectin, ghrelin, or family history of type 2 diabetes. A significantly lower proportion of Pro/Ala patients had hirsutism and they had on average lower hirsutism scores than Pro/Pro patients. No relationship was found between the Pro/Ala polymorphism and other signs of hyperandrogenism.

Conclusion  The Pro12Ala polymorphism of the PPARγ gene is associated with increased insulin sensitivity and lower hirsutism scores in PCOS women.

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