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Association study to evaluate Foxo1 and Foxo3 gene polymorphisms in polycystic ovary syndrome: a preliminary case–control study and in silico analysis

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Abstract

Background

Polycystic ovary syndrome (PCOS) is known as a multifactorial and multi-gene-mediated endocrine disorder among women of reproductive age. FoxO1 and FoxO3 are members of the forkhead transcriptional factors family that play a pivotal role in the function of ovaries. The current work is aimed at investigating the association between gene variants of FoxO1 and FoxO3 and the risk of PCOS in a sample of the Iranian population.

Methods and results

We recruited 200 women diagnosed with PCOS and 200 healthy women. Both polymerase PCR–RFLP and ARMS-PCR methods were used for genotyping. Sanger sequencing was recruited to confirm the genotyping results. The T allele of rs17592236 and the C allele of rs12585277 decreased PCOS risk by 29 and 28%, respectively. In contrast, the C allele of rs2253310 and G allele of rs2802292 increased the risk of PCOS by 1.39 and 1.63 folds, correspondingly. Bioinformatics results showed that some genes, including matrix metallopeptidase 9 (MMP-9), phosphoinositide-3-Kinase Regulatory Subunit 224 1 (PIK3R1), peroxisome proliferator-activated receptor Gamma (PPARG), and glycogen synthase 225 kinase-3 beta (GSK-3 beta) have significant interactions with FoxO1, suggesting that FoxO1 might have crucial roles in regulating different signaling pathways in ovarian cells.

Conclusion

We found that FoxO1 rs17592236C > T and rs12585277C > T had a protective role against PCOS, while FoxO3 rs2253310C > G and rs2802292G > T  enhanced the risk of this metabolic disorder in our population. Additional studies on larger populations with varying races are needed to confirm these findings.

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Data availability

The data in this manuscript are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank the technical staff of the Cellular & Molecular Research Center, Zahedan University of Medical Sciences, for their support.

Funding

The current study received no funding.

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Authors and Affiliations

  1. Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran

    Arghavan Rakhshani Nejad & Saeedeh Samareh Moosavi

  2. Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran

    Saman Sargazi, Milad Heidari Nia & Ramin Saravani

  3. Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

    Marzieh Ghasemi

  4. Moloud Infertility Center, Ali Ibn Abitaleb Hospital, Zahedan University of Medical Sciences, Zahedan, Iran

    Marzieh Ghasemi

  5. Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Ramin Saravani

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  1. Arghavan Rakhshani Nejad
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Contributions

Conceptualization, SS; Clinical assessments: MG; writing-original draft preparation, AR, MHN, MS-M and SS; writing-review and editing, SS, MHN; supervision, SS, RS. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Saman Sargazi.

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The ethics committee of Mashhad University of Medical Sciences (Ethical code: IR.MUMS.REC.1400.375) approved the protocol of the current study.

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Rakhshani Nejad, A., Sargazi, S., Ghasemi, M. et al. Association study to evaluate Foxo1 and Foxo3 gene polymorphisms in polycystic ovary syndrome: a preliminary case–control study and in silico analysis. Mol Biol Rep 50, 3569–3580 (2023). https://doi.org/10.1007/s11033-023-08292-w

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