Skip to main content
Log in

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia

  • Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance.

Methods

The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR–restriction fragment length polymorphism (RLFP) assay.

Results

No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected.

Conclusion

The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Azziz R, Carmina E, Dewailly D et al (2006) Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab 91(11):4237–4245

    Article  CAS  PubMed  Google Scholar 

  2. Carmina E, Lobo RA (1999) Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 84:1897–1899

    Article  CAS  PubMed  Google Scholar 

  3. Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800

    Article  CAS  PubMed  Google Scholar 

  4. Ovalle F, Azziz R (2002) Insulin resistance, polycystic ovary syndrome, and type II diabetes mellitus. Fertil Steril 77(6):1095–1105

    Article  PubMed  Google Scholar 

  5. Dunaif A, Segal KR, Futterweit W, Dorjansky A (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38:1164–1174

    Article  Google Scholar 

  6. Kahn CR (1994) Banting lecture: insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 43:1066–1084

    Article  CAS  PubMed  Google Scholar 

  7. Venkatesan AM, Dunaif A, Corbould A (2001) Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res 56:295–308

    Article  CAS  PubMed  Google Scholar 

  8. Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P, Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB 15:2099–2111

    Article  CAS  Google Scholar 

  9. Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald SM, Pedersen O (1993) Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes. Lancet 342:828–832

    Article  CAS  PubMed  Google Scholar 

  10. Hitman GA, Hawrami K, McCarthy MI et al (1995) Insulin receptor substrate-1 gene mutations in NIDDM: implications for the study of polygenic disease. Diabetologia 38:481–486

    Article  CAS  PubMed  Google Scholar 

  11. McGettrick AJ, Feeners EP, Kahn CR (2005) Human Insulin receptor substrate-1 (IRS-1) polymorphism G972S causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. JBC 280(8):6441–6446

    Article  CAS  Google Scholar 

  12. El Mkadem SA, Lautier C, Macari F et al (2001) Role of allelic variants G972S of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes 50:2164–2168

    Article  CAS  PubMed  Google Scholar 

  13. Villuendas G, Botella-Carretero JI, Roldán B, Sancho J, Escobar-Morreale HF, San Millán JL (2005) Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. Hum Reprod 20(11):3184–3191

    Article  CAS  PubMed  Google Scholar 

  14. Ehrmann DA, Tang X, Yoshiuchi I, Cox NJ, Bell GI (2002) Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic features of polycystic ovary syndrome. J Clin Endocrinol Metab 87(9):4297–4300

    Article  CAS  PubMed  Google Scholar 

  15. Sir-Petermann T, Pérez-Bravo F, Angel B, Maliqueo M, Calvillan M, Palomino A (2001) G972S polymorphism of the IRS-1 in women with polycystic ovary syndrome. Diabetologia 44(9):1200–1201

    Article  CAS  PubMed  Google Scholar 

  16. Zawadski JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome. In: Dunaif A, Givens JR, Haseltine FP, Merriam GE (eds) Polycystic ovary syndrome. Blackwell, Boston, pp 377–384

    Google Scholar 

  17. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on the diagnostic criteria and long term health risks related to polycystic ovary syndrome. Fertil Steril 81(1): 19–25

    Google Scholar 

  18. Mathews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and B cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  Google Scholar 

  19. Carmina E, Lobo RA (2004) Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome. Fertil Steril 82:661–665

    Article  PubMed  Google Scholar 

  20. Bezerra RM, de Castro V, Sales T et al (2002) The G972S Polymorphism in insulin receptor substrate-1 is associated with decreased birth weight in a population- based sample of Brazilian newborns. Diabetes Care 25:550–553

    Article  CAS  PubMed  Google Scholar 

  21. Norman RJ, Dewailly D, Legro RS, Hickey TE (2007) Polycystic ovary syndrome. Lancet 370:685–697

    Article  CAS  PubMed  Google Scholar 

  22. Holte J, Berg T, Berne C, Berglund L, Lithell H (1994) Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab 78:1052–1058

    Article  CAS  PubMed  Google Scholar 

  23. Araki E, Myra AL, Patti M et al (1994) Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372:186–189

    Article  CAS  PubMed  Google Scholar 

  24. Brüning JC, Winnay J, Cheatham B, Kahn CR (1997) Differential signalling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1 deficient mice. Mol Cell Biol 17:1513–1521

    PubMed  Google Scholar 

  25. Urbanek M, Legro RS, Driscoll DA et al (1999) Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA 96:8573–8587

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George L. Adonakis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marioli, D.J., Koika, V., Adonakis, G.L. et al. No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia. Arch Gynecol Obstet 281, 1045–1049 (2010). https://doi.org/10.1007/s00404-009-1299-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-009-1299-2

Keywords

Navigation