, Volume 30, Issue 1, pp 19–26 | Cite as

The role of genes and environment in the etiology of PCOS

  • Evanthia Diamanti-Kandarakis
  • Helen Kandarakis
  • Richard S. LegroEmail author


Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor dietary choices and physical inactivity, worsens PCOS in susceptible individuals. The role of other environmental modifiers such as infectious agents or toxins are speculative. Phenotype confusion has characterized genetic studies of PCOS. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, the follistatin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin recept or gene (but not involving this gene), as it has been identified in two separate studies, and perhaps most importantly has not yet been refuted by larger studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. To date, no gene has been identified that causes or contributes substantially to the development of a PCOS phenotype.

Key Words

Insulin resistance familial studies association studies linkage obesity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Zawadski, J. K. and Dunaif, A. (1992). In: Polycystic ovary syndrome Blackwell Scientific Boston.Google Scholar
  2. 2.
    Balen, A. H., Laven, J. S., Tan, S. L., and Dewailly, D. (2003). Hum. Reprod. Update 9, 505–514.PubMedCrossRefGoogle Scholar
  3. 3.
    Jonard, S., Robert, Y., and Dewailly, D. (2005). Hum. Reprod. 20, 2893–2898.PubMedCrossRefGoogle Scholar
  4. 4.
    Rotterdam ESHRE/ASRM sponsored PCOS consensus work-shop group (2004). Hum. Reprod. 19, 41–47.Google Scholar
  5. 5.
    Abbott, D. H., Dumesic, D. A., and Franks, S. (2002). J. Endocrinol. 174, 1–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Legro, R. S., Driscoll, D., Strauss, J. F., et al. (1998). Proc. Natl. Acad. Sci. USA 95, 14956–14960.PubMedCrossRefGoogle Scholar
  7. 7.
    Jahanfar, S., Eden, J. A., Warren, P., et al. (1995). Fertil. Steril. 63, 478–486.PubMedGoogle Scholar
  8. 8.
    Jahanfar, S., Maleki, H., Mosavi, A. R., and Jahanfar, M. (2004). Gynecol. Endocrinol. 18 327–334.PubMedCrossRefGoogle Scholar
  9. 9.
    Vink, J. M., Sadrzadeh, S., Lambalk, C. B., and Boomsma, D. I. (2006). J. Clin. Endocrinol. Metab. 91, 2100–2104.PubMedCrossRefGoogle Scholar
  10. 10.
    Lander, E. S. and Schork, N. J. (1994). Science 265, 2037–2048 (erratum, 266, 353).PubMedCrossRefGoogle Scholar
  11. 11.
    Cardon, L. R. and Bell, J. I. (2001). Nat. Rev. Genet. 2, 91–99.PubMedCrossRefGoogle Scholar
  12. 12.
    Ehrmann, D. A., Schwarz, P. E., Hara, M., et al. (2001). J. Clin. Endocrinol. Metab. 87, 1669–1673.CrossRefGoogle Scholar
  13. 13.
    El Mkadem, S. A., Lautier, C., Macari, F., et al. (2001). Diabetes 50, 2164–2168.PubMedCrossRefGoogle Scholar
  14. 14.
    Cousin, P., Calemard-Michel, L., Lejeune, H., et al. (2004). J. Clin. Endocrinol. Metab. 89, 917–924.PubMedCrossRefGoogle Scholar
  15. 15.
    Carey, A. H., Chan, K. L., Short, F., et al. (1993). Clin. Endocrinol. 38, 653–658.Google Scholar
  16. 16.
    Gharani, N., Waterworth, D. M., Williamson, R., and Franks, S. (1996). J. Clin. Endocrinol. Metab. 81, 4174.PubMedCrossRefGoogle Scholar
  17. 17.
    Spielman, R. S. and Ewens, W. J. (1996). Am. J. Hum. Genet. 59, 983–989.PubMedGoogle Scholar
  18. 18.
    Urbanek, M., Woodroffe, A., Ewens, K. G., et al. (2005). J. Clin. Endocrinol. Metab. 90, 6623–6629.PubMedCrossRefGoogle Scholar
  19. 19.
    Urbanek, M., Legro, R. S., Driscoll, D. A., et al. (1999). Proc. Natl. Acad. Sci. USA 96, 8573–8578.PubMedCrossRefGoogle Scholar
  20. 20.
    Urbanek, M., Wu, X., Vickery, K. R., et al. (2000). J. Clin. Endocrinol. Metab. 85, 4455–4461.PubMedCrossRefGoogle Scholar
  21. 21.
    Gharani, N., Waterworth, D. M., Batty, S., et al. (1997). Hum. Mol. Genet. 6, 397–402.PubMedCrossRefGoogle Scholar
  22. 22.
    Diamanti-Kandarakis, E., Bartzis, M. I., Bergiele, A. T., et al. (2000). Fertil. Steril. 73, 735–741.PubMedCrossRefGoogle Scholar
  23. 23.
    San Millan, J. L., Sancho, J., Calvo, R. M., and Escobar-Morreale, H. F. (2001). Fertil. Steril. 75, 797–802.PubMedCrossRefGoogle Scholar
  24. 24.
    Gaasenbeek, M., Powell, B. L., Sovio, U., et al. (2004). J. Clin. Endocrinol. Metab. 89, 2408–2413.PubMedCrossRefGoogle Scholar
  25. 25.
    Legro, R. S., Bentley-Lewis, R., Driscoll, D., et al. (2002). J. Clin. Endocrinol. Metab. 87, 2128–2133.PubMedCrossRefGoogle Scholar
  26. 26.
    Cresswell, J. L., Barker, D. J., Osmond, C., et al. (1997). Lancet. 350, 1131–1135.PubMedCrossRefGoogle Scholar
  27. 27.
    Ibanez, L., Potau, N., Francois, I., and de Zegher, F. (1998). J. Clin. Endocrinol. Metab. 83, 3558–3562.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim, L. H., Taylor, A. E., and Barbieri, R. L. (2000). Fertil. Steril. 73, 1097–1098.PubMedCrossRefGoogle Scholar
  29. 29.
    Kiddy, D. S., Hamilton-Fairley, D., Bush, A., et al. (1992). Clin. Endocrinol. 36, 105–111.Google Scholar
  30. 30.
    Carmina, E., Legro, R. S., Stamets, K., et al. (2003). Hum. Reprod. 18, 2289–2293.PubMedCrossRefGoogle Scholar
  31. 31.
    Stamets, K., Taylor, D. S., Kunselman, A., et al. (2004). Fertil. Steril. 81, 630–637.PubMedCrossRefGoogle Scholar
  32. 32.
    Moran, L. J., Noakes, M., Clifton, P. M., et al. (2003). J. Clin. Endocrinol. Metab. 88, 812–819.PubMedCrossRefGoogle Scholar
  33. 33.
    Pelletier, C., Imbeault, P., and Tremblay, A. (2003). Obes. Rev. 4, 17–24.PubMedCrossRefGoogle Scholar
  34. 34.
    Steinmetz, R., Young, P. C., Caperell-Grant, A., et al. (1996). Cancer Res. 56, 5403–5409.PubMedGoogle Scholar
  35. 35.
    Dewailly, E., Dodin, S., Verreault, R., et al. (1994). J. Natl. Cancer Inst. 86, 232–234.PubMedCrossRefGoogle Scholar
  36. 36.
    Isojarvi, J. I., Laatikainen, T. J., Pakarinen, A. J., et al. (1993). N. Engl. J. Med. 329, 1383–1388.PubMedCrossRefGoogle Scholar
  37. 37.
    Isojarvi, J. I., Rattya, J., Myllyla, V. V., et al. (1998). Ann. Neurol. 43, 446–451.PubMedCrossRefGoogle Scholar
  38. 38.
    Dhurandhar, N. V. (2004). Drug News Perspect. 17, 307–313.PubMedCrossRefGoogle Scholar
  39. 39.
    Dhurandhar, N. V., Whigham, L. D., Abbott, D. H., et al. (2002). J. Nutr. 132, 3155–3160.PubMedGoogle Scholar
  40. 40.
    Dhurandhar, N. V., Kulkarni, P. R., Ajinkya, S. M., et al. (1997). Obes. Res. 5, 464–469.PubMedGoogle Scholar
  41. 41.
    Cooper, H. E., Spellacy, W. N., Prem, K. A., and Cohen, W. D. (1968). Am. J. Obstet. Gynecol. 100, 371–387.PubMedGoogle Scholar
  42. 42.
    Wilroy, R. S. Jr., Givens, J. R., Wiser, W. L., et al. (1975). Birth Defects Orig. Artic. Ser. 11, 81–85.PubMedGoogle Scholar
  43. 43.
    Ferriman, D. and Purdie, A. W. (1979). Clin. Endocrinol. 11, 291–300.Google Scholar
  44. 44.
    Hague, W. M., Adams, J., Reeders, S. T., et al. (1988). Clin. Endocrinol. 29, 593–605.Google Scholar
  45. 45.
    Lunde, O., Magnus, P., Sandvik, L., and Hoglo, S. (1989). Gynecol. Obstet. Invest. 28, 23–30.PubMedCrossRefGoogle Scholar
  46. 46.
    Norman, R. J., Masters, S., and Hague, W. (1996). Fertil. Steril. 66, 942–947.PubMedGoogle Scholar
  47. 47.
    Govind, A., Obhrai, M. S. and Clayton, R. N. (1999). J. Clin. Endocrinol. Metab. 84, 38–43.PubMedCrossRefGoogle Scholar
  48. 48.
    Kahsar-Miller, M. D., Nixon, C., Boots, L. R., et al. (2001). Fertil. Steril. 75, 53–58.PubMedCrossRefGoogle Scholar
  49. 49.
    Legro, R. S., Kunselman, A. R., Demers, L., et al. (2002). J. Clin. Endocrinol. Metab. 87, 2134–2138.PubMedCrossRefGoogle Scholar
  50. 50.
    Sir-Petermann, T., Angel, B., Maliqueo, M., et al. (2002). Diabetologia 45, 959–964.PubMedCrossRefGoogle Scholar
  51. 51.
    Yildiz, B. O., Yarali, H., Oguz, H., and Bayraktar, M. (2003). J. Clin. Endocrinol. Metab. 88, 2031–2036.PubMedCrossRefGoogle Scholar
  52. 52.
    Kaushal, R., Parchure, N., Bano, G., et al. (2004). Clin. Endocrinol. (Oxf.) 60, 322–328.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Evanthia Diamanti-Kandarakis
    • 1
  • Helen Kandarakis
    • 1
  • Richard S. Legro
    • 1
    Email author
  1. 1.Endocrine Section, First Department of MedicineUniversity of Athens Medical SchoolAthensGreece

Personalised recommendations