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Variation analysis of anti-Müllerian hormone gene in Chinese women with polycystic ovary syndrome

  • Endocrine Genetics/Epigenetics
  • Published:
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Abstract

Purpose

Anti-Müllerian hormone (AMH) is crucial for folliculogenesis. Prenatal exposure to AMH in mice produces a phenocopy of polycystic ovary syndrome (PCOS) in the adult female offspring. The aim of this study was to determine whether genetic variation in AMH gene contribute to PCOS in women of Chinese ancestry.

Methods

We conducted a case–control genetic study in 383 PCOS case and 433 control women of Chinese ancestry. The exons and the 5′ flanking region of AMH were sanger sequenced. Bioinformatic prediction of variant deleteriousness was performed.

Results

Seven novel heterozygous variants along with 15 rare known variants in AMH were identified in women with PCOS but not in controls. The novel variants included one frameshift variant (c.125_129delACTTG), one synonymous variant (c.1095C>T), one variant (c.-14T>C) in the 5’-untranslated region (UTR), four variants(c.-775C>T, c.-682C>T, c.-333A>G, c.-137A>T) in 5′ flanking sequence. Of all the AMH variants identified in women with PCOS, eight were predicted to be deleterious by bioinformatic analysis. The PCOS carriers of predicted-to-be-deleterious PCOS-specific AMH variants had increased total follicle numbers compared to PCOS noncarriers (p = 0.021).

Conclusions

Our findings suggest the AMH plays a role in the development of PCOS. The exact mechanisms by which the predicted-to-be-deleterious novel and rare AMH variants described in our study affect AMH function requires further study.

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Data availability

All the data generated and analyses during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Yuehong Bian, Shizhen Su for their technical assistance. They appreciate Zhao Wang, Changming Zhang, Ying Wang, and Xin Zhang, for sample collection. The authors also thank all the patients who participated in this study.

Funding

This study was supported by the National Key Research and Development Program of China (2017YFC1001000), the National Natural Science Foundation of China (31871509, 81622021, 31571548, 31601199), the US National Institutes of Health grants (R01 HD085227) and the Foundation for Distinguished Young Scholars of Shandong Province (JQ201816).

Author information

Authors and Affiliations

  1. Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Lang Qin, Shigang Zhao, Ping Yang, Yongzhi Cao, Jiangtao Zhang, Zi-Jiang Chen & Han Zhao

  2. Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China

    Lang Qin, Shigang Zhao, Ping Yang, Yongzhi Cao, Jiangtao Zhang, Zi-Jiang Chen & Han Zhao

  3. Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China

    Lang Qin, Shigang Zhao, Ping Yang, Yongzhi Cao, Jiangtao Zhang, Zi-Jiang Chen & Han Zhao

  4. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China

    Lang Qin, Shigang Zhao, Ping Yang, Yongzhi Cao, Jiangtao Zhang, Zi-Jiang Chen & Han Zhao

  5. National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China

    Lang Qin, Shigang Zhao, Ping Yang, Yongzhi Cao, Jiangtao Zhang, Zi-Jiang Chen & Han Zhao

  6. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Zi-Jiang Chen

  7. Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Andrea Dunaif

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  1. Lang Qin
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  8. Han Zhao
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Contributions

H.Z., A.D., and Z-J.C. designed, supported the study; Y.Z.C. and J.T.Z. collected clinical data and blood samples; L.Q. performed experiments; L.Q, S.G.Z., and P.Y analyzed the data; L.Q. drafted the manuscript; H.Z. and A.D. revised the article. All authors gave their final approval of the version to be published.

Corresponding authors

Correspondence to Zi-Jiang Chen, Andrea Dunaif or Han Zhao.

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The authors declare that they have no conflict of interest.

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Written informed consent was obtained from all participants.

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All the authors have reviewed the final version of the manuscript and approved the publication of the manuscript.

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The study was approved by the institutional review board of Reproductive Medicine, Shandong University.

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Qin, L., Zhao, S., Yang, P. et al. Variation analysis of anti-Müllerian hormone gene in Chinese women with polycystic ovary syndrome. Endocrine 72, 287–293 (2021). https://doi.org/10.1007/s12020-020-02538-4

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