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The possible effects of the MTOR polymorphisms on preeclampsia susceptibility, severity, and onset: a case–control study and in silico analysis

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Abstract

Background

Preeclampsia (PE) is a gestational complication with developed hypertension and proteinuria. Evidence showed the role of mTOR in various cellular processes. Therefore, this study aimed to evaluate the effects of MTOR polymorphisms on susceptibility, severity, and onset of Preeclampsia (PE).

Methods and results

A total of 250 PE pregnant women and 258 age-matched control subjects were recruited in this study. To genotype MTOR polymorphisms, the PCR-RFLP method was used. The SpliceAid 2 and PROMO tools were used for in silico analysis. The maternal MTOR rs17036508T/C polymorphism was associated with PE risk in various genetic models. There was no relationship between rs2536T/C and rs2295080T/G polymorphisms and PE. The TTC and TGC haplotypes of rs2536/ rs2295080/ rs17036508 polymorphisms were significantly higher in PE women. Subgroup analysis revealed the association between the MTOR rs2295080 variant and an increased risk of Early-onset PE (EOPE). However, the MTOR rs17036508 was associated with a higher risk of EOPE and Late- Onset PE. In addition, the MTOR rs2295080 could increase the risk of severe PE. The results of the in silico analysis showed that rs17036508 disrupted several binding motifs in the mutant sequence. The PROMO database revealed that the T to C substitution leads to the loss of the TFII-I binding site in the mutant allele.

Conclusion

The MTOR rs17036508T/C polymorphism was associated with PE risk. There was an association between the MTOR rs2295080 variant and an increased risk of EOPE. The MTOR rs17036508T/C and rs2295080T/C variants could disrupt several binding motifs and TFII-I binding respectively.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Abbreviations

PE:

Preeclampsia

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

EOPE:

Early-onset preeclampsia

LOPE:

Late-onset preeclampsia

Sam68:

Src associated in mitosis, of 68 kDa

hnRNP G:

Heterogeneous nuclear ribonucleoprotein G

ETR-3:

Elav-type RNA-binding protein

TFII-I:

Transcription factor II-I

PI3K/AKT/mTOR:

Phosphoinositide-3 kinase-AKT-mammalian target of the rapamycin

SNP:

Single nucleotide polymorphism

EVT:

Extravillous trophoblast

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Funding

This article was extracted from a PhD dissertation at Zahedan University of Medical Sciences (IR.ZAUMS.REC.1399.349). Financial support was received from Iran National Science Foundation (INSF, project No 98023121) to conduct this study.

Author information

Authors and Affiliations

  1. Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran

    Mahnaz Rezaei, Mohsen Saravani & Saeedeh Salimi

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

    Mahnaz Rezaei, Mohsen Saravani & Hossein Shahraki-Ghadim

  3. Department of Obstetrics and Gynecology, Pregnancy Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

    Marzieh Ghasemi & Fatemeh Ghahghayi

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

    Marzieh Ghasemi

  5. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Saeedeh Salimi

Authors
  1. Mahnaz Rezaei
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  2. Marzieh Ghasemi
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  3. Mohsen Saravani
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  4. Fatemeh Ghahghayi
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  5. Hossein Shahraki-Ghadim
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  6. Saeedeh Salimi
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by MR, MG, FG, MS and SS. In silico analysis was performed by HS-G. The first draft of the manuscript was written by MR and SS. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Saeedeh Salimi.

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Conflict of interest

All authors declare no conflict of interest to disclosure.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was approved by the ethics committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1399.349).

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Rezaei, M., Ghasemi, M., Saravani, M. et al. The possible effects of the MTOR polymorphisms on preeclampsia susceptibility, severity, and onset: a case–control study and in silico analysis. Mol Biol Rep 51, 335 (2024). https://doi.org/10.1007/s11033-023-09190-x

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