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Seyed Abutorabi E, Hossein Rashidi B, Irani S, Haghollahi F, Bagheri M. Investigation of the FSHR, CYP11, and INSR Mutations and Polymorphisms in Iranian Infertile Women with Polycystic Ovary Syndrome (PCOS). rbmb.net 2021; 9 (4) :470-477
URL: http://rbmb.net/article-1-527-en.html
URL: http://rbmb.net/article-1-527-en.html
Elaheh Seyed Abutorabi 
, Batool Hossein Rashidi * , Shiva Irani , Fedyeh Haghollahi , Maryam Bagheri
, Batool Hossein Rashidi * , Shiva Irani , Fedyeh Haghollahi , Maryam Bagheri
Vali-e-Asr Reproductive Health Research center, Tehran University of Medical Sciences, Tehran, Iran
Abstract: (3435 Views)
Introduction: polycystic ovary syndrome (PCOS) is the most common cause of ovarian dysfunction associated with infertility, Oligomenorrhea or amenorrhea, hirsutism, acne, and obesity. A large body of evidence unraveled, three major groups of genes play critical roles in underlying PCOS molecular mechanism. The aim of this study is to investigate critical exonic variant of FSHR, CYP11, and INSR and determine the functionality of these mutations in Iranian patients with PCOS.
Materials and methods: In this case-control study, 130 patients with PCOS who referred to the Vali-e-Asr Hospital with infertility were included. 3 ml peripheral blood was taken from the participants for DNA extraction. PCR was conducted for each gene and the PCR product was genotyped by sequencing.
Results: The data showed that there were two polymorphisms in INSR genes which did not change the protein sequences; these alterations can also be considered as a single nucleotide polymorphism (SNP). Moreover, any exonic variant has not been detected in CYP11B1. Whereas, two missense mutation have been detected in FSHR gene including p.Ala307Thr and p. Asn680Ser. It has been shown that the polymorphisms of the FSHR gene affect the hormone response in the ovaries. Our data demonstrated that the FSHR mutations frequencies were higher in the patients with PCOS rather than control people (without any infertility complication) significantly.
Conclusion: Altogether, our data showed that the polymorphisms of FSHR were significantly associated with PCOS in Iranian infertile women. Further studies with larger sample sizes are needed to be performed in order to explore the strength of the association.
Materials and methods: In this case-control study, 130 patients with PCOS who referred to the Vali-e-Asr Hospital with infertility were included. 3 ml peripheral blood was taken from the participants for DNA extraction. PCR was conducted for each gene and the PCR product was genotyped by sequencing.
Results: The data showed that there were two polymorphisms in INSR genes which did not change the protein sequences; these alterations can also be considered as a single nucleotide polymorphism (SNP). Moreover, any exonic variant has not been detected in CYP11B1. Whereas, two missense mutation have been detected in FSHR gene including p.Ala307Thr and p. Asn680Ser. It has been shown that the polymorphisms of the FSHR gene affect the hormone response in the ovaries. Our data demonstrated that the FSHR mutations frequencies were higher in the patients with PCOS rather than control people (without any infertility complication) significantly.
Conclusion: Altogether, our data showed that the polymorphisms of FSHR were significantly associated with PCOS in Iranian infertile women. Further studies with larger sample sizes are needed to be performed in order to explore the strength of the association.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2020/07/9 | Accepted: 2020/08/2 | Published: 2021/03/8
Received: 2020/07/9 | Accepted: 2020/08/2 | Published: 2021/03/8
References
1. Prapas N, Karkanaki A, Prapas I, Kalogiannidis I, Katsikis I, Panidis D. Genetics of polycystic ovary syndrome. Hippokratia. 2009;13(4):216-23.
2. Melo AS, Ferriani RA, Navarro PA. Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice. Clinics (Sao Paulo). 2015;70(11):765-9. [DOI:10.6061/clinics/2015(11)09]
3. Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016;37(5):467-520. [DOI:10.1210/er.2015-1104] [PMID] [PMCID]
4. Shaaban Z, Khoradmehr A, Jafarzadeh Shirazi MR, Tamadon A. Pathophysiological mechanisms of gonadotropins- and steroid hormones-related genes in etiology of polycystic ovary syndrome. Iran J Basic Med Sci. 2018;22(1):3-16.
5. Urbanek M. The genetics of the polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007;3(2):103-11. [DOI:10.1038/ncpendmet0400] [PMID]
6. Mykhalchenko K, Lizneva D, Trofimova T, Walker W, Suturina L, Diamond MP, et al. Genetics of polycystic ovary syndrome. Expert Rev Mol Diagn. 2017;17(7):723-733. [DOI:10.1080/14737159.2017.1340833] [PMID]
7. Strauss JF. [Epidemiology and genetics of polycystic ovary syndrome: recent date]. J Gynecol Obstet Biol Reprod (Paris). 2003;32(3 Pt 2):S11-6.
8. Amato P, Simpson JL. The genetics of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):707-18. [DOI:10.1016/j.bpobgyn.2004.05.002] [PMID]
9. Simoni M, Tempfer CB, Destenaves B, Fauser BC. Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response. Hum Reprod Update. 2008;14(5):459-84. [DOI:10.1093/humupd/dmn024] [PMID] [PMCID]
10. 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. Reprod Biol Endocrinol. 2014;12:86. [DOI:10.1186/1477-7827-12-86] [PMID] [PMCID]
11. Conti M. Specificity of the cyclic adenosine 3′, 5′-monophosphate signal in granulosa cell function. Biol Reprod. 2002;67(6):1653-61. [DOI:10.1095/biolreprod.102.004952] [PMID]
12. Behre HM, Greb RR, Mempel A, Sonntag B, Kiesel L, Kaltwasser P, et al. Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genomics. 2005;15(7):451-6. [DOI:10.1097/01.fpc.0000167330.92786.5e] [PMID]
13. Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Hum Reprod. 2007;22(4):1031-6. [DOI:10.1093/humrep/del457] [PMID]
14. Franks S, McCarthy M. Genetics of ovarian disorders: polycystic ovary syndrome. Rev Endocr Metab Disord. 2004;5(1):69-76. [DOI:10.1023/B:REMD.0000016125.05878.96] [PMID]
15. Jin L, Zhu XM, Luo Q, Qian Y, Jin F, Huang HF. A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS. Mol Hum Reprod. 2006;12(3):151-5. [DOI:10.1093/molehr/gal022] [PMID]
16. Schuring AN, Schulte N, Sonntag B, Kiesel L. Androgens and insulin--two key players in polycystic ovary syndrome. Recent concepts in the pathophysiology and genetics of polycystic ovary syndrome. Gynakol Geburtshilfliche Rundsch. 2008;48(1):9-15. [DOI:10.1159/000111465] [PMID]
17. Mukherjee S, Maitra A. Molecular & genetic factors contributing to insulin resistance in polycystic ovary syndrome. Indian J Med Res. 2010;131:743-60.
18. Fica S, Albu A, Constantin M, Dobri GA. Insulin resistance and fertility in polycystic ovary syndrome. J Med Life. 2008;1(4):415-22.
19. Ramezani Tehrani F, Daneshpour M, Hashemi S, Zarkesh M, Azizi F. Relationship between polymorphism of insulin receptor gene, and adiponectin gene with PCOS. Iran J Reprod Med. 2013;11(3):185-94.
20. Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2-10. [DOI:10.1016/j.clinbiochem.2018.03.012] [PMID]
21. Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30(1):19-26. [DOI:10.1385/ENDO:30:1:19]
22. Chapman JC, Min SH, Freeh SM, Michael SD. The estrogen-injected female mouse: new insight into the etiology of PCOS. Reprod Biol Endocrinol. 2009;18;7:47. [DOI:10.1186/1477-7827-7-47] [PMID] [PMCID]
23. Santana LF, Ferriani RA, Sa MF, Reis RM. [Treatment of infertility in women with polycystic ovary syndrome]. Rev Bras Ginecol Obstet. 2008;30(4):201-9. [DOI:10.1590/S0100-72032008000400008] [PMID]
24. Zhao MX, Zhou GY, Zhu JY, Gong B, Hou JX, Zhou T, et al. Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women. Biomed Environ Sci. 2015;28(9):696-700.
25. Andre GM, Martins Trevisan C, Pedruzzi IN, Fernandes RFM, Oliveira R, Christofolini DM, et al. The Impact of FSHR Gene Polymorphisms Ala307Thr and Asn680Ser in the Endometriosis Development. DNA Cell Biol. 2018;37(6):584-591. [DOI:10.1089/dna.2017.4093] [PMID]
26. Rod A, Jarzabek K, Wolczynski S, Benhaim A, Reznik Y, Denoual-Ziad C. ESR1 and FSHR gene polymorphisms influence ovarian response to FSH in poor responder women with normal FSH levels. Endocrinol Metab Synd. 2014;3:1-5. [DOI:10.4172/2161-1017.1000141]
27. Andre GM, Martins Trevisan C, Pedruzzi IN, Fernandes RFM, Oliveira R, Christofolini DM, et al. The impact of FSHR gene polymorphisms Ala307Thr and Asn680Ser in the endometriosis development. DNA and cell biology. 2018;37(6):584-591. [DOI:10.1089/dna.2017.4093] [PMID]
28. Huang X, Li L, Hong L, Zhou W, Shi H, Zhang H, et al. The Ser680Asn polymorphism in the follicle‐stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation. Clin Endocrinol (Oxf). 2015;82(4):577-83. [DOI:10.1111/cen.12573] [PMID]
29. Mohiyiddeen L, Newman WG, Cerra C, McBurney H, Mulugeta B, Roberts SA, et al. A common Asn680Ser polymorphism in the follicle-stimulating hormone receptor gene is not associated with ovarian response to gonadotropin stimulation in patients undergoing in vitro fertilization. Fertil Steril. 2013;99(1):149-155. [DOI:10.1016/j.fertnstert.2012.08.037] [PMID]
30. Mohiyiddeen L, Newman WG, McBurney H, Mulugeta B, Roberts SA, Nardo LG. Follicle-stimulating hormone receptor gene polymorphisms are not associated with ovarian reserve markers. Fertil Steril. 2012;97(3):677-81. [DOI:10.1016/j.fertnstert.2011.12.040] [PMID]
31. Wu X-q, Xu S-m, Liu J-f, Bi X-y, Wu Y-x, Liu J. Association between FSHR polymorphisms and polycystic ovary syndrome among Chinese women in north China. J Assist Reprod Genet. 2014;31(3):371-7. [DOI:10.1007/s10815-013-0166-z] [PMID] [PMCID]
32. Unsal T, Konac E, Yesilkaya E, Yilmaz A, Bideci A, Onen HI, et al. Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome. J Assist Reprod Genet. 2009;26(4):205-16. [DOI:10.1007/s10815-009-9308-8] [PMID] [PMCID]
33. Du J, Zhang W, Guo L, Zhang Z, Shi H, Wang J, 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):292-5. [DOI:10.1016/j.ymgme.2010.03.018] [PMID]
34. 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):925-30. [DOI:10.1007/s10815-011-9619-4] [PMID] [PMCID]
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