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Molecular determination of progesterone receptor’s PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS)

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Abstract

Polycystic ovary syndrome, previously known as Stein–Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk of PCOS. It has a prevalence of 6–20% among the reproductive-age women. Progesterone is a key hormone in the pathophysiology of PCOS and patients show diminished response (progesterone resistance), implicating the role of progesterone receptor (PR) as a factor in the disease etiology and prognosis. In this case–control study, we have used mutation-specific PCR (confirmed by Sanger sequencing) to detect the presence of a pathologically significant PR polymorphic variant called as PROGINS. The variant has an Alu insertion in intron G and has two SNPs in exon 4 and exon 5, with all the three aberrations in complete disequilibrium. Our results demonstrated a statistically significant difference in the frequencies of PROGINS between the PCOS patients and healthy controls (p = 0.047). The frequencies of the genotypes CC (A1/A1), CT (A1/A2), and TT (A2/A2) in patients were 74.50%, 20.58%, and 4.90%, and in healthy controls they were 87.28%, 11%, and 1.69%, respectively. Our results put forward two determining factors with regard to PCOS: (i) the frequency of PROGINS allele was significantly higher among PCOS patients compared to the healthy matched controls (0.15 vs 0.07) in the studied population, (ii) the PROGIN allele was significantly associated with the lower levels of serum progesterone in PCOS patients (p < 0.003). The findings are conspicuous as these relate the PROGINS variant to the increased susceptibility of PCOS and might explain the progesterone resistance in patients.

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Acknowledgements

The authors acknowledge the Prince Fahd Research chair, University of Tabuk, for research facility.

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Authors and Affiliations

  1. Prince Fahd Research Chair, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia

    Rashid Mir, Jameel Barnawi, Faisel M. Abuduhier & Mohammad Fahad Ullah

  2. Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia

    Rashid Mir, Malik A. Altayar, Abdullah Hamadi, Faris J. Tayeb, Nizar H. Saeedi, Mohammed M. Jalal, Jameel Barnawi, Faisel M. Abuduhier & Mohammad Fahad Ullah

  3. Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Hail, Hail, Saudi Arabia

    Sanad E. Alshammari

  4. Laboratory of Human Genome and Multifactorial Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia

    Nabil Mtiraoui

  5. King Salman Military Hospital, Tabuk, Saudi Arabia

    Mohammed Eltigani M. Ali

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  1. Rashid Mir
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  2. Malik A. Altayar
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  12. Mohammad Fahad Ullah
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Correspondence to Mohammad Fahad Ullah.

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The authors declare that they have no conflict of interest.

Human and animal rights

All procedures with regard to the sampling and study of human specimens were followed in accordance with the Helsinki Declaration of 1975 as revised in 2013 (http://ethics.iit.edu/ecodes/node/3931).

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The study has an institutional ethical approval with informed consent for genome-wide studies on PCOS.

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Mir, R., Altayar, M.A., Hamadi, A. et al. Molecular determination of progesterone receptor’s PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS). Mamm Genome 33, 508–516 (2022). https://doi.org/10.1007/s00335-021-09941-w

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  • DOI: https://doi.org/10.1007/s00335-021-09941-w

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