Relationship of follicle stimulating hormone receptor gene Thr307Ala polymorphism with polycystic ovary syndrome in Iraqi women

AJBM crossMark
American Journal of BioMedicine Volume 9, Issue 2, pages 142-153

Zainab Kadhim Abed1, Estabraq AR. Al-Wasiti*2, Ban Abbas Abdulmajeed3, Nawfal Kamel Khiro4


Polycystic ovary syndrome (PCOS) is a polygenic multifactorial status affecting millions of females worldwide. It is a common cause of anovulatory subfertility. Because of follicle stimulating hormone (FSH), is an important agent in human reproduction. Therefore, the correlation between follicle stimulating hormone receptor (FSHR) gene polymorphisms and polycystic ovary syndrome attracts broad attention. The objective of this study is to investigate the potential association between the follicle stimulating hormone receptor gene Thr307Ala polymorphism with polycystic ovary syndrome in the Iraqi women. A case-control study including 135 Iraqi women of Arab ethnicity (75 PCOS patients and 60 age-matched control women). The age of subjects ranged from 18 to 38 years. PCOS diagnosis was established by Rotterdam consensus criteria. The FSHR (Thr307Ala) variant was tested by conventional polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) followed by deoxyribonucleic acid (DNA) sequencing. The heterozygote Thr/Ala (AG) genotype of Thr307Ala (rs6165) polymorphism of follicle stimulating hormone receptor gene was giving a significant risk (odds ratio=19.4, 95%CI=1.14-30.40, P value=0.002) of developing PCOS in Iraqi women compared with control group. Sequencing analysis of DNA confirms RFLP analysis. In conclusion; the variant Thr307Ala (rs6165) of the follicle stimulating hormone receptor gene is associated with polycystic ovary syndrome and may consider as the causal factor of polycystic ovary syndrome in Iraqi women.

Keywords:PCOS; FSHR geneThr307Ala polymorphism; Women

Copyright © 2019 by The American Society for BioMedicine and BM-Publisher, Inc.

Article citationReferencesFull-Text/PDFBecome reviewer
The citation data is computed by the following citation measuring services:

Cited by (CrossRef)
Google Scholar

  1. Jacob S, Tang TH, Balen AH. Polycystic Ovary Syndrome and Assisted Reproduction. In :Gradner DK, Weissman A, Howles CM, Shoham Z ,editors. Textbook of Assisted Reproductive Technologies, Volume Two: Clinical Perspective.5th ed. London: CRC Press; 2018. pp. 762-772.
  2. Ding T, Hardiman PJ, Petersen I, et al. The Prevalence of Polycystic Ovary Syndrome in Reproductive-Aged Women of Different Ethnicity: A Systematic Review and Meta-Analysis. Oncotarget. 2017;8(56):96351-96358.
  3. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 Consensus on Diagnostic Criteria and Long-Term Health Risks Related to Polycystic Ovary Syndrome. Fertility and Sterility.2004;81:19-25.
  4. Fauser BC, Tarlatzis BC, Rebar RW, et al .Consensus on Women's Health Aspects of Polycystic Ovary Syndrome (PCOS): The Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertility and Sterility. 2012;97(1):28-38.
  5. Kosova G, Urbanek M. Genetics of the Polycystic Ovary Syndrome. Molecular and Cellular Endocrinology. 2013; 373(1-2):29-38.
  6. De Melo AS, Dias SV, Cavalli Rde C, et al. Pathogenesis of Polycystic Ovary Syndrome: Multifactorial Assessment from the Foetal Stage to Menopause. Reproduction. 2015;150(1):R11-24.
  7. De Leo V, Musacchio MC, Cappelli V, et al. Genetic, Hormonal and Metabolic Aspects of PCOS: An Update. Reproductive Biology and Endocrinology. 2016;14:38.
  8. Cui L, Li G, Zhong W, et al. Polycystic ovary syndrome susceptibility single nucleotide polymorphisms in women with a single PCOS clinical feature. Human Reproduction. 2015; 30(3):732-736.
  9. Feng C, Lv PP, Yu TT, et al. The association between polymorphism of INSR and polycystic ovary syndrome: a meta-analysis. International journal of molecular sciences. 2015;16(2):2403-2425.
  10. Peng CY, Xie HJ, Guo ZF, et al. The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis. Journal of assisted reproduction and genetics. 2014; 31(9):1211-9.
  11. Liu AL, Xie HJ, Xie HY, et al. Association between Fat Mass and Obesity Associated (FTO) Gene Rs9939609 A/T Polymorphism and Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. BMC Medical Genetics. 2017;18(1):89.
  12. Zhao S, Tian Y, Gao X, et al. Family-Based Analysis of Eight Susceptibility Loci in Polycystic Ovary Syndrome. Scientific Reports. 2015; 5:12619.
  13. Chen ZJ, Zhao H, He L, et al. Genome-Wide Association Study Identifies Susceptibility Loci for Polycystic Ovary Syndrome on Chromosome 2p16.3, 2p21 and 9q33.3. Nature Genetics. 2011; 43(1):55-59.
  14. Mutharasan P, Galdones E, Peñalver Bernabé B, et al. Evidence for Chromosome 2p16.3 Polycystic Ovary Syndrome Susceptibility Locus in Affected Women of European Ancestry. The Journal of Clinical Endocrinology & Metabolism. 2013;98(1):185-190.
  15. Busch AS, Hagen CP, Almstrup K, et al. Genetic Variations Altering FSH Action Affect Circulating Hormone Levels as Well as Follicle Growth in Healthy Peripubertal Girls. Human Reproduction. 2016;31(4):897-904.
  16. Simoni M, Nieschlag E, Gromoll J. Isoforms and Single Nucleotide Polymorphisms of the FSH Receptor Gene: Implications for Human Reproduction. Human Reproduction Update. 2002;8(5):413-421.
  17. Ulloa-Aguirre A, Zariñán T. The Follitropin Receptor: Matching Structure and Function. Molecular Pharmacology. 2016;90(5):596-608.
  18. Desai SS, Roy BS, Mahale SD. Mutations and Polymorphisms in FSH Receptor: Functional Implications in Human Reproduction. Reproduction. 2013;146(6):R235-248.
  19. Kene PS, Dighe RR, Mahale SD. Delineation of Regions in the Extracellular Domain of Follicle-Stimulating Hormone Receptor Involved in Hormone Binding and Signal Transduction. American Journal of Reproductive Immunology. 2005;54:38-48.
  20. Kuijper EA, Blankenstein MA, Luttikhof LJ, et al. Frequency Distribution of Polymorphisms in the FSH Receptor Gene in Infertility Patients of Different Ethnicity. Reproductive Biomedicine Online. 2010;20:588-593.
  21. Laan M, Grigorova M, Huhtaniemi IT. Pharmacogenetics of Follicle-Stimulating Hormone Action. Current Opinion in Endocrinology, Diabetes and Obesity. 2012;19(3):220-227.
  22. Sambrook J, Fritsch EF, Maniatis T. Gel electrophoresis of DNA. In: Sambrook J, Fritsch EF, Maniatis T. (Eds.) Molecular Cloning: a Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA.1989.Chapter 6.
  23. Sundblad V, Chiauzzi VA, Escobar ME, et al. Screening of FSH Receptor Gene in Argentine Women with Premature Ovarian Failure (POF). Molecular and Cellular Endocrinology. 2004;222(1-2):53-59.
  24. Wu XQ, Xu SM, Liu JF, et al. Association between FSHR Polymorphisms and Polycystic Ovary Syndrome among Chinese Women in North China. Journal of Assisted Reproduction and Genetics. 2014;31:371-377.
  25. Jonard S, Dewailly D. The Follicular Excess in Polycystic Ovaries, Due to Intra-Ovarian Hyperandrogenism, May be the Main Culprit for the Follicular Arrest. Human Reproduction Update. 2004;10(2):107-117.
  26. Abdel-Aziz AF, El-Sokkary AMA, El-Refaeey AA, El-Sokkary MMA, Osman HG, El-Saeed RA. Association between Follicle Stimulating Hormone Receptor (FSHR) Polymorphism and Polycystic Ovary Syndrome among Egyptian Women. International Journal of Biochemistry Research & Review 2015;5(3):198-206.
  27. Khafagi Z, Mozdarani H, Behmanesh M, et al. Distribution of FSHR, ESR1 and ESR2 SNPs among Women with Polycystic Ovary Syndrome Undergoing in Vitro Fertilization. Bulletin of Environment, Pharmacology and Life Sciences. 2014; 3(8):128-134.
  28. 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. Journal of Assisted Reproduction and Genetics. 2011;28(10):925-930.
  29. Sudo S, Kudo M, Wada S, et al. Genetic and Functional Analyses of Polymorphisms in the Human FSH Receptor Gene. Molecular Human Reproduction. 2002;8(10):893-899.
  30. Kim JJ, Choi YM, Hong MA, et al. FSH Receptor Gene P. Thr307Ala and P. Asn680Ser Polymorphisms are Associated with the Risk of Polycystic Ovary Syndrome. Journal of Assisted Reproduction and Genetics. 2017;34:1087-1093.
  31. Unsal T, Konac E, Yesilkaya E, et al. Genetic Polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 Genes in Adolescent Girls with Polycystic Ovary Syndrome. Journal of Assisted Reproduction and Genetics. 2009;26:205-216.
  32. Fu L, Zhang Z, Zhang A, et al. Association Study between FSHR Ala307Thr and Ser680Asn Variants and Polycystic Ovary Syndrome (PCOS) in Northern Chinese Han Women. Journal of Assisted Reproduction and Genetics. 2013;30:717-721.
  33. Singhasena W, Pantasri T, Piromlertamorn W, Samchimchom S, Vutyavanich T. Follicle-Stimulating Hormone Receptor Gene Polymorphism in Chronic Anovulatory Women, with or without Polycystic Ovary Syndrome: A Cross-Sectional Study. Reproductive Biology and Endocrinology. 2014;12:86.
  34. Kambalachenu H, Paul S, Nellepalli S, Venkatachalam P. Study on Follicle Stimulating Hormone Receptor Gene Polymorphisms in South Indian Women with Polycystic Ovarian Syndrome. American Medical Journal. 2013;4:160-167.
  35. Baban ASS, Korsheed SH, Al Hayawi AY. The FSHR Polymorphisms Association with Polycystic Ovary Syndrome in Women of Erbil, Kurdistan in North of Iraq. Ibn AL-Haitham Journal for Pure and Applied Science. 2018;262-272.
  36. Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up‐regulation of FAK-PI 3 K/A kt pathway. Cell biology international 2014;38:85-91.
  37. Shaikh N, Dadachanji R, Mukherjee S. Genetic Markers of Polycystic Ovary Syndrome: Emphasis on Insulin Resistance. International Journal of Medical Genetics. 2014;(2014):10.
  38. Merkin SS, Phy JL, Sites CK, et al. Environmental Determinants of Polycystic Ovary Syndrome. Fertility and Sterility. 2016;106(1):16-24.
  39. Louwers YV, Stolk L, Uitterlinden AG, et al. Cross-Ethnic Meta-Analysis of Genetic Variants for Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism. 2013;98(12):E2006-E2012.
  40. Engmann L, Jin S, Sun F, et al. Racial and Ethnic Differences in the Polycystic Ovary Syndrome Metabolic Phenotype. American Journal of Obstetrics and Gynecology. 2017;216(5):493.e1-493.e13.
  41. Yau TT, Ng NY, Cheung LP, et al. Polycystic Ovary Syndrome: A Common Reproductive Syndrome with Long-Term Metabolic Consequences. Hong Kong Medical Journal. 2017;23(6):622-634.

Who Can Become a Reviewer?
Any expert in the article's research field can become a reviewer with American Journal of Biomedicine. Editors might ask you to look at a specific aspect of an article,...

Find out more


Research Article
American Journal of BioMedicine Volume 9, Issue 2, pages 142-153
Received March 23, 2021; revised May 21, 2021; accepted June 02, 2021; published June 22, 2021

PDF Download this Paper

How to cite this article
Abed ZK, Al-Wasiti ER, Abdulmajeed BA, Khiro NK. Relationship of follicle stimulating hormone receptor Gene Thr307Ala polymorphism with polycystic ovary syndrome in Iraqi women. American Journal of BioMedicine 2021;9(2):142-153.
Research Article
1. Abstract
2. Keywords
3. Introduction
4. Methods
5. Results
6. Discussion
7. References

Article metric