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Genetic Basis of Metabolic Abnormalities in Polycystic Ovary Syndrome

Implications for Therapy

  • Genomics in Health and Disease
  • Published:
American Journal of Pharmacogenomics

Abstract

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder characterized by hyperandrogenism and chronic anovulation. The syndrome is frequently associated with an increased risk for insulin resistance and type 2 diabetes mellitus; obesity exacerbates insulin resistance and favors the progression from impaired glucose tolerance to diabetes in these patients. In young women, precocious pubarche and hyperinsulinemia are early manifestations of PCOS.

The familial clustering of women with PCOS suggests that heredity is implicated in the origin of the syndrome. However, genetic approaches to its pathogenesis have been hampered by the heterogeneity of phenotypic features within families, and the lack of uniform criteria for diagnosis.

Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptibility and protective genomic variants under the influence of environmental factors. Both linkage analysis and association studies are valid tools for the study of the genetics of PCOS.

Candidate genes for PCOS include those related to androgenic pathways and metabolic associations of the syndrome. More recently, genes encoding inflammatory cytokines have been identified as target genes for PCOS, as proinflammatory genotypes and phenotypes are also associated with obesity, insulin resistance, type 2 diabetes, PCOS, and increased cardiovascular risk.

This paper reviews the candidate genes involved in the metabolic pathways that are altered in patients with PCOS. Despite a significant amount of research in this area, none of the genes studied so far has been identified as the PCOS susceptibility gene for the majority of cases. PCOS is the first component of the metabolic syndrome to be detected in many women, so the identification and correct diagnosis of PCOS has important preventive and therapeutic implications for the affected women and their families. In the future, new therapeutic approaches to PCOS will rely on knowing the genes, environmental influences, and etiologic mechanisms associated with the disorder.

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Acknowledg ments

Belén Roldán Martín is a postdoctoral fellow of the Fundación Ramón Areces, Madrid. This work was supported in part by Grants FIS 02/0741 and RGDM G03/212 from the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo, and Grant CAM 08.6/0010/2001 from the Consejería de Educación, Comunidad de Madrid, Spain. ## The authors have no conflicts of interest directly relevant to the content of this review.

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  1. Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar Km 9’1, Madrid, E-28034, Spain

    Belén Roldán &  Héctor F. Escobar-Morreale

  2. Departments of Molecular Genetics, Hospital Ramón y Cajal, Madrid, Spain

    José L. San Millán

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  1. Belén Roldán
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  2. José L. San Millán
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  3. Héctor F. Escobar-Morreale
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Correspondence to Héctor F. Escobar-Morreale.

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Roldán, B., Millán, J.L.S. & Escobar-Morreale, H.F. Genetic Basis of Metabolic Abnormalities in Polycystic Ovary Syndrome. Am J Pharmacogenomics 4, 93–107 (2004). https://doi.org/10.2165/00129785-200404020-00004

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