Skip to main content
SpringerLink
Log in

Genetic Polymorphisms in Pakistani Women With Polycystic Ovary Syndrome

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone β (fshrβ), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone β (lhβ), estrogen receptor α (esr1), and estrogen receptor β (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r2 value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome. Etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4):219–231.

    Article  CAS  Google Scholar 

  2. Brassard M, AinMelk Y, Baillargeon JP. Basic infertility including polycystic ovary syndrome. Med Clin North Am. 2008;92(5): 1163–1192.

    Article  CAS  Google Scholar 

  3. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181–91.

    Article  Google Scholar 

  4. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–47.

    Article  Google Scholar 

  5. de Castro F, Ruiz R, Montoro L, et al. Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril. 2003; 80(3):571–576.

    Article  Google Scholar 

  6. Jun JK, Yoon JS, Ku SY, et al. Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet. 2006;51(8): 665–670.

    Article  CAS  Google Scholar 

  7. Tong Y, Liao WX, Roy AC, Ng SC. Association of AccI polymorphism in the follicle-stimulating hormone beta gene with polycystic ovary syndrome. Fertil Steril. 2000;74(6):1233–1236.

    Article  CAS  Google Scholar 

  8. Yang CQ, Chan KY, Ngan HY, et al. Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility. Carcinogenesis. 2006; 27(7):1502–1506.

    Article  CAS  Google Scholar 

  9. Urbanek M. The genetics of the polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007;3(2):103–111.

    Article  CAS  Google Scholar 

  10. Gharib SD, Wierman ME, Shupnik MA, Chin WW. Molecular biology of pituitary gonadotropins. Endocr Rev. 1990;11(1): 177–199.

    Article  CAS  Google Scholar 

  11. Moyle WR, Campbell RK. Gonadotropins. In: Adashi EY, Rock JA, Rosenwalks Z, eds. Reprod Endocrinol Surg Technol. Philadelphia: Lippincott-Raven; 1996; 683–724.

    Google Scholar 

  12. Shi Y, Zhao H, Cao Y, et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet. 2012;44(9):1020–1025.

    Article  CAS  Google Scholar 

  13. Mutharasan P, Galdones E, Penalver B, et al. Evidence for chromosome 2p 16.3 polycystic ovary susceptibility locus in affected women of European ancestry. J Clin Endocrinol Metab. 2013;98(1):E185–E190.

    Article  CAS  Google Scholar 

  14. Dolfin E, Guani B, Lussiana C, Mari C, Restagno G, Revelli A. FSH-receptor Ala307Thr polymorphism is associated to polycystic ovary syndrome and to a higher responsiveness to exogenous FSH in Italian women. J Assist Reprod Genet. 2011;28(10): 925–930.

    Article  Google Scholar 

  15. Du J, Zhang W, Guo L, et al. Two FSHR variants, haplotypes and meta-analysis in Chinese women with premature ovarian failure and polycystic ovary syndrome. Mol Genet Metab. 2010;100(3): 292–295.

    Article  CAS  Google Scholar 

  16. Bon-Hee GU, Jung-MI P, Kwang-Hyun B. Genetic variations of follicle stimulating hormone receptor are associated with polycystic ovary syndrome. Int J Mol Medc. 2010;26(1):107–112.

    Google Scholar 

  17. Livshyts G, Podlesnaja S, Kravchenko S, Sudoma I, Livshits L. A distribution of two SNPs in exon 10 of the FSHR gene among the women with a diminished ovarian reserve in Ukraine. J Assist Reprod Genet. 2009;26:29–34.

    Article  Google Scholar 

  18. Orio FJ, Ferrarini E, Cascella T, et al. Genetic analysis of the follicle stimulating hormone receptor gene in women with polycystic ovary syndrome. J Endocrinol Invest. 2006;29(11):975–982.

    Article  CAS  Google Scholar 

  19. Hegele-Hartung C, Siebel P, Peters O, et al. Impact of isotypeselective estrogen receptor agonists on ovarian function. Proc Natl Acad Sci. 2004;101(14):5129–5134.

    Article  CAS  Google Scholar 

  20. Jakimiuk AJ, Weitsman SR, Yen HW, Bogusiewicz M, Magoffin DA. Estrogen receptor alpha and beta expression in theca and granulosa cells from women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(12):5532–5538.

    Article  CAS  Google Scholar 

  21. Yariz KO, Walsh T, Uzak A, et al. Inherited mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in empty follicle syndrome. Fertil Steril. 2011;96(2):e1250–e1230.

    Article  Google Scholar 

  22. Balen AH. Hypersecretion of luteinizing hormone and the polycystic ovary syndrome. Hum Reprod. 1993;8(suppl 2):123–128.

    Article  CAS  Google Scholar 

  23. Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685–697.

    Article  CAS  Google Scholar 

  24. Huhtaniemi I, Alevizaki M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab. 2006;20:561–576.

    Article  CAS  Google Scholar 

  25. Huhtaniemi IT, Themmen AP. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine. 2005;26(3):207–217.

    Article  CAS  Google Scholar 

  26. Sambrook J, Fritschi EF, Maniatis T. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, 1989.

    Google Scholar 

  27. Hawley ME, Kidd KK. HAPLO, a program using the EM algorithm to estimate the frequencies of multi-site haplotypes. J Heredity. 1995;86(5):409–411.

    Article  CAS  Google Scholar 

  28. Dempster AP, Laird NM, Rubin DB. Maximum likelihood from incomplete data via the EM algorithm. J Royal Stat Soc Series. 1977;39(1):1–22.

    Google Scholar 

  29. Li L, Yang D, Chen X, Chen Y, Feng S, Wang L. Clinical and metabolic features of polycystic ovary syndrome. Int J Obstet Gynecol. 2007;97(2):129–134.

    Article  CAS  Google Scholar 

  30. Shi Y, Guo M, Yan J, et al. Analysis of clinical characteristics in large-scale Chinese women with polycystic ovary syndrome. Neuro Endocrinol Lett. 2007;28(6):807–810.

    CAS  PubMed  Google Scholar 

  31. Liu N, Ma Y, Wang S, et al. Association of the genetic variants of luteinizing hormone, luteinizing hormone receptor and polycystic ovary syndrome. Reprod Biol Endocrinol. 2012;10:36.

    Article  CAS  Google Scholar 

  32. Tong Y, Liao WX, Roy AC, Ng SC. Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome. Horm Metab Res. 2001;33(4): 221–226.

    Article  CAS  Google Scholar 

  33. Liao WX, Tong Y, Roy AC, Ng SC. New AccI polymorphism in the follicle-stimulating hormone beta-subunit gene and its prevalence in three Southeast Asian populations. Hum Hered. 1999; 49(3):181–182.

    Article  CAS  Google Scholar 

  34. La Marca A, Papaleo E, Alviggi C, et al. The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age. Hum Reprod. 2013;28(5):1369–1374.

    Article  Google Scholar 

  35. Lamminen T, Huhtaniemi I. A common genetic variant of luteinizing hormone; relation to normal and aberrant pituitary–gonadal function. Eur J Pharmacol. 2001;414(1):1–7.

    Article  CAS  Google Scholar 

  36. Lamminen T, Jiang M, Manna PR, et al. Functional study of a recombinant form of human LHβ-subunit variant carrying the Gly102Ser mutation found in Asian populations. Mol Hum Reprod. 2002;8(10):887–892.

    Article  CAS  Google Scholar 

  37. Takahashi K, Karino K, Kanasaki H, et al. Influence of missense mutation and silent mutation of LHb-subunit gene in Japanese patients with ovulatory disorders. Eur J Hum Gen. 2003;11(5): 402–408.

    Article  CAS  Google Scholar 

  38. Nectaria X, Leandros L, Ioannis G, Agathocles T. The importance of ERa and ERb gene polymorphisms in PCOS. Gynecol Endocrinol. 2012;28(7):505–508.

    Article  CAS  Google Scholar 

  39. Sundarrajan C, Liao WX, Roy AC, Ng SC. Association between estrogen receptor-beta gene polymorphisms and ovulatory dysfunctions in patients with menstrual disorders. J Clin Endocrinol Metab. 2001;86(1):135–139.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Zoology, GC University Lahore, Lahore, Pakistan

    Irfana Liaqat & Nusrat Jahan PhD

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    Irfana Liaqat, Graciela Krikun PhD & Hugh S. Taylor PhD

Authors
  1. Irfana Liaqat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nusrat Jahan PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graciela Krikun PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hugh S. Taylor PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irfana Liaqat.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liaqat, I., Jahan, N., Krikun, G. et al. Genetic Polymorphisms in Pakistani Women With Polycystic Ovary Syndrome. Reprod. Sci. 22, 347–357 (2015). https://doi.org/10.1177/1933719114542015

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114542015

Keywords

Search

Navigation