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Anti-Müllerian hormone gene polymorphism is associated with androgen levels in Chinese polycystic ovary syndrome patients with insulin resistance

  • Genetics
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The objective of the study was to investigate whether genetic polymorphisms of the anti-Müllerian hormone (AMH) and its specific receptor anti-Müllerian hormone type II receptor (AMHRII) were associated with the hormone disorder and phenotype of polycystic ovary syndrome (PCOS).

Methods

This case-control study included 141 PCOS patients and 123 normal women. Two polymorphisms of AMH and AMHRII and the clinical characteristics of participants such as body mass index (BMI), serum luteinizing hormone (LH), estradiol levels (E2), total testosterone levels (T), and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed with the case-control sample. Gene–gene interactions of AMH and AMHRII genes were analyzed based multifactor-dimensionality reduction method.

Results

A significant difference of AMH gene polymorphisms were observed in IR-PCOS women and controls. The AMH and AMHRII gene polymorphisms were not found a significant difference in non-IR-PCOS and normal groups. To IR-PCOS women, genotypes of AMH were closely related to the serum levels of LH (P = 0.000), testosterone (P = 0.000) and HOMA-IR (P = 0.038), while in the non-IR-PCOS and normal groups, no relationship was found. No impact of AMH and AMHRII gene–gene interactions was demonstrated.

Conclusions

Our research suggests that the diversity of AMH genotypes in the AMH signal pathway may be connected with the susceptibility and phenotype of PCOS with insulin resistance.

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References

  1. Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol. 2014;10(10):624–36. doi:10.1038/nrendo.2014.102.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Antimullerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril. 2002;77(2):357–62. doi:10.1038/345167a0.

    Article  PubMed  Google Scholar 

  4. van Rooij IA, Broekmans FJ, Te VE, Fauser BC, Bancsi LF, de Jong FH, et al. Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod. 2002;17(12):3065–71.

    Article  PubMed  Google Scholar 

  5. Peluso C, Fonseca FL, Rodart IF, Cavalcanti V, Gastaldo G, Christofolini DM, et al. AMH: An ovarian reserve biomarker in assisted reproduction. Clin Chim Acta. 2014;437:175–82. doi:10.1016/j.cca.2014.07.029.

    Article  CAS  PubMed  Google Scholar 

  6. Durlinger AL, Visser JA, Themmen AP. Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction. 2002;124(5):601–9.

    Article  CAS  PubMed  Google Scholar 

  7. Gruijters MJ, Visser JA, Durlinger AL, Themmen AP. Anti-Mullerian hormone and its role in ovarian function. Mol Cell Endocrinol. 2003;211(1–2):85–90.

    Article  CAS  PubMed  Google Scholar 

  8. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR, Matzuk MM, et al. Anti-Mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology. 2001;142(11):4891–9. doi:10.1210/endo.142.11.8486.

    CAS  PubMed  Google Scholar 

  9. Visser JA, Durlinger AL, Peters IJ, van den Heuvel ER, Rose UM, Kramer P, et al. Increased oocyte degeneration and follicular atresia during the estrous cycle in anti-Mullerian hormone null mice. Endocrinology. 2007;148(5):2301–8. doi:10.1210/en.2006-1265.

    Article  CAS  PubMed  Google Scholar 

  10. Homburg R, Crawford G. The role of AMH in anovulation associated with PCOS: a hypothesis. Hum Reprod. 2014;29(6):1117–21. doi:10.1093/humrep/deu076.

    Article  CAS  PubMed  Google Scholar 

  11. Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(3):941–5. doi:10.1210/jc.2005-2076.

    Article  CAS  PubMed  Google Scholar 

  12. Homburg R, Ray A, Bhide P, Gudi A, Shah A, Timms P, et al. The relationship of serum anti-Mullerian hormone with polycystic ovarian morphology and polycystic ovary syndrome: a prospective cohort study. Hum Reprod. 2013;28(4):1077–83. doi:10.1093/humrep/det015.

    Article  CAS  PubMed  Google Scholar 

  13. Urbanek M. The genetics of the polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007;3(2):103–11. doi:10.1038/ncpendmet0400.

    Article  CAS  PubMed  Google Scholar 

  14. Kevenaar ME, Laven JS, Fong SL, Uitterlinden AG, de Jong FH, Themmen AP, et al. A functional anti-mullerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients. J Clin Endocrinol Metab. 2008;93(4):1310–6. doi:10.1210/jc.2007-2205.

    Article  CAS  PubMed  Google Scholar 

  15. Kevenaar ME, Themmen AP, Laven JS, Sonntag B, Fong SL, Uitterlinden AG, et al. Anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. Hum Reprod. 2007;22(6):1547–54. doi:10.1093/humrep/dem036.

    Article  CAS  PubMed  Google Scholar 

  16. Tian CH, Hu R, Jia ST, Lan SX, Tian JS, Wang FM. Association between gene polymorphism of Anti-mullerian hormone and its type receptor II and ovarian reserve. Acta Med Univ Sci Technol Huazhong. 2012;41(03):315–9.

    CAS  Google Scholar 

  17. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–7.

  18. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. doi:10.1016/S0140-6736(07)61602-X.

    Article  Google Scholar 

  19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.

    Article  CAS  PubMed  Google Scholar 

  20. Xing X, Yang W, Yang Z. The diagnostic significance of homeostasismodel assessment of insulin resistance in metabolic syndrome among subjects with different glucose tolerance. Chin J Diabetes. 2004;12(03):31–5.

    Google Scholar 

  21. Sproul K, Jones MR, Mathur R, Azziz R, Goodarzi MO. Association study of four key folliculogenesis genes in polycystic ovary syndrome. BJOG. 2010;117(6):756–60. doi:10.1111/j.1471-0528.2010.02527.x.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Drummond AE. The role of steroids in follicular growth. Reprod Biol Endocrinol. 2006;4:16. doi:10.1186/1477-7827-4-16.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Havelock JC, Rainey WE, Carr BR. Ovarian granulosa cell lines. Mol Cell Endocrinol. 2004;228(1–2):67–78. doi:10.1016/j.mce.2004.04.018.

    Article  CAS  PubMed  Google Scholar 

  24. Young JM, McNeilly AS. Theca: the forgotten cell of the ovarian follicle. Reproduction. 2010;140(4):489–504. doi:10.1530/REP-10-0094.

    Article  CAS  PubMed  Google Scholar 

  25. Wen X, Li D, Tozer AJ, Docherty SM, Iles RK. Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles. Reprod Biol Endocrinol. 2010;8:117. doi:10.1186/1477-7827-8-117.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Chang HM, Klausen C, Leung PC. Antimullerian hormone inhibits follicle-stimulating hormone-induced adenylyl cyclase activation, aromatase expression, and estradiol production in human granulosa-lutein cells. Fertil Steril. 2013;100(2):585–92. doi:10.1016/j.fertnstert.2013.04.019.

    Article  CAS  PubMed  Google Scholar 

  27. Detti L, Uhlmann RA, Lu M, Diamond MP, Saed GM, Fletcher NM, et al. Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age. J Assist Reprod Genet. 2013;30(11):1421–9. doi:10.1007/s10815-013-0087-x.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Homburg R. Androgen circle of polycystic ovary syndrome. Hum Reprod. 2009;24(7):1548–55. doi:10.1093/humrep/dep049.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. Buckler HM, Phillips SE, Cameron IT, Healy DL, Burger HG. Vaginal progesterone administration before ovulation induction with exogenous gonadotropins in polycystic ovarian syndrome. J Clin Endocrinol Metab. 1988;67(2):300–6. doi:10.1210/jcem-67-2-300.

    Article  CAS  PubMed  Google Scholar 

  31. Baillargeon JP, Carpentier A. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity. Fertil Steril. 2007;88(4):886–93. doi:10.1016/j.fertnstert.2006.12.055.

    Article  CAS  PubMed  Google Scholar 

  32. Neagu M, Cristescu C. Anti-Mullerian hormone--a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome. J Med Life. 2012;5(4):462–4.

    PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81260109/H0425), the Program for Special talents of Ningxia medical university (XT201421), the program of Ningxia Medical University (220–2001090105), the project on science and social development of Jiangsu (BE2012706), the Top Six Talent Peaks Program of Jiangsu (2014-WSW-080), and the National Science Foundation of Yangzhou (YZ2014050).

Authors’ contributions

Meng-Xue Zheng and Yan Li participated in study design, performed the experiments, and drafted the manuscript. Rong Hu participated in study design, directed the execution of experiments, and revised the article critically for intellectual content. Fei-Miao Wang participated in sample collection and performed statistical analysis. Xiao-Mei Zhang and Bing Guan participated in mentoring and critical discussion. All authors approved the final version of the manuscript.

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Correspondence to Rong Hu.

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The authors declare that they have no competing interests. The manuscript has been reviewed and approved by all authors, and state that the manuscript has not been previously published, and is not being considered for publication by another journal.

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Capsule

AMH genetic polymorphism in the AMH signal pathway is related to serum androgen levels in Chinese PCOS with insulin resistance.

Meng-Xue Zheng and Yan Li contributed equally to this work.

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Zheng, MX., Li, Y., Hu, R. et al. Anti-Müllerian hormone gene polymorphism is associated with androgen levels in Chinese polycystic ovary syndrome patients with insulin resistance. J Assist Reprod Genet 33, 199–205 (2016). https://doi.org/10.1007/s10815-015-0641-9

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  • DOI: https://doi.org/10.1007/s10815-015-0641-9

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