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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The authors declare no conflict of interest.
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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.
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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