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Association of SRD5A2 gene mutations with risk of hypospadias in the Iranian population

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Abstract

Background

Hypospadias is one of the most common forms of congenital malformation of the male external genitalia worldwide. The ratio in the Iranian population is one in 250 live male births. The conversion of testosterone to dihydrotestosterone (DHT) in the presence of steroid 5α-reductase 2, which is encoded by SRD5A2 gene, plays an important role in the normal development of the male reproductive system.

Methods

We examined whether SRD5A2 gene mutations (V89L and A49T polymorphisms) are associated with the risk of hypospadias in the Iranian population. We performed exons sequencing for SRD5A2 gene in 109 hypospadias patients.

Results

We identified two new mutations in the subgroups of affected cases: including a substitution of the nucleotide T > A in the codon 73 [c.219T > A (p.Leu73_Ser74insHisPro)] and an insertion of an extra A nucleotide in the codon 77 [c.229insA* (p.Gly77*)]. Additionally, we performed PCR–RFLP for the two identified polymorphisms and revealed that V89L [OR = 5.8, 95% CI (3.8–8.8), p value < 0.001] and A49T [OR = 10.16, 95% CI (3.94–26.25), p value < 0.001] are significantly associated with hypospadias occurrence in patients. Our haplotype analysis further indicated that the Leu–Ala haplotype increases risk of hypospadias; conversely, the Val–Ala haplotype decreases the risk of hypospadias in the studied patients.

Conclusions

This study demonstrates that polymorphisms in the SRD5A2 gene could be considered as a risk factor for hypospadias disease emergence.

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Acknowledgements

We are grateful to the medical staff of Mofid Hospital for collecting samples. This study was supported by a grant from the Research Dean of Shahid Beheshti University of Medical Sciences.

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    Authors and Affiliations

    1. Department of Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar St., Daneshjoo Blvd., Evin, Chamran Highway, Tehran, Iran

      M. Rahimi, Z. Fazeli, R. Mirfakhraie & M. D. Omrani

    2. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

      M. Ghanbari

    3. Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

      M. Ghanbari

    4. Department of Pediatric Surgery, Mofid Children’s Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

      M. Rouzrokh

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

      S. Omrani

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    Correspondence to R. Mirfakhraie or M. D. Omrani.

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    The authors declare no conflict of interest.

    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

    Informed consent

    This informed consent form collected from parents of children between 1 and 4 years of age who attended to Mofid Children’s Hospital, and who were asking to participate in the study.

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    R. Mirfakhraie, M. D. Omrani have contributed equally to this work.

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    Rahimi, M., Ghanbari, M., Fazeli, Z. et al. Association of SRD5A2 gene mutations with risk of hypospadias in the Iranian population. J Endocrinol Invest 40, 391–396 (2017). https://doi.org/10.1007/s40618-016-0573-y

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    • DOI: https://doi.org/10.1007/s40618-016-0573-y

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