Advertisement

PEX10, SIRPA-SIRPG, and SOX5 gene polymorphisms are strongly associated with nonobstructive azoospermia susceptibility

  • Xiuli GuEmail author
  • Honggang Li
  • Xi Chen
  • Xue Zhang
  • Fen Mei
  • Mingzhu Jia
  • Chengliang XiongEmail author
Genetics
  • 24 Downloads

Abstract

Purpose

Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. A previous Chinese genome-wide single-nucleotide polymorphism (SNP) association studies have identified four SNPs (rs12097821 in PRMT6 gene, rs2477686 in PEX10 gene, rs6080550 in SIRPA-SIRPG, and rs10842262 in SOX5 gene) as being significantly associated with risk factors for nonobstructive azoospermia (NOA). However, the results were not fully repeated in later studies, which calls for further investigations.

Methods

We here performed a case-control study in a central Chinese population to explore the association between the four SNPs and male infertility, which included 631 infertile men (NOA and oligozoospermia) and 720 healthy fertile men. The genotyping was performed using the polymerase chain reaction–restriction fragment length polymorphism and confirmed by sequencing.

Results

The results showed that rs12097821 and rs10842262 were strongly associated with the risk of NOA but not total male infertility or oligozoospermia, while rs2477686 and rs6080550 were not associated with the risk of total male infertility, NOA, or oligozoospermia. To improve the statistical strength, a meta-analysis was conducted. The results suggested that rs2477686, rs6080550, and rs10842262 were significantly associated with male infertility, especially with NOA, while rs12097821 was only found to be associated with total male infertility.

Conclusions

Collectively, the rs2477686, rs6080550, and rs10842262 may indeed be the genetic risk factors for NOA, which requires further investigation using larger independent sets of samples in different ethnic populations.

Keywords

Single-nucleotide polymorphism (SNP) Male infertility Han Chinese Meta-analysis 

Notes

Acknowledgments

The authors thank all the participants and investigators enrolled in this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Mclachlan RI, de Kretser DM. Male infertility: the case for continued research. Med J Aust. 2001;174(3):116–7.Google Scholar
  2. 2.
    Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15(6):369–84.CrossRefGoogle Scholar
  3. 3.
    DS D, AM B. The genetics of male infertility. J Urol. 2009;27(02):124–36.Google Scholar
  4. 4.
    Ferlin A, Foresta C. New genetic markers for male infertility. Curr Opin Obstet Gynecol. 2014;26(3):193–8.CrossRefGoogle Scholar
  5. 5.
    Hu Z, Xia Y, Guo X, Dai J, Li H, Hu H, et al. A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nat Genet. 2012;44(2):183–6.CrossRefGoogle Scholar
  6. 6.
    Sato Y, Jinam T, Iwamoto T, Yamauchi A, Imoto I, Inoue I, et al. Replication study and meta-analysis of human nonobstructive azoospermia in Japanese populations. Biol Reprod. 2013;88(4):87.Google Scholar
  7. 7.
    Tu W, Liu Y, Shen Y, Yan Y, Wang X, Yang D, et al. Genome-wide loci linked to non-obstructive azoospermia susceptibility may be independent of reduced sperm production in males with normozoospermia. Biol Reprod. 2015;92(2):41.CrossRefGoogle Scholar
  8. 8.
    Liu F, Liu Y, Bao J, Jin R, Bai G, Tang D, et al. Relationship between PRMT6, PEX10, SOX5 and CYP19 gene polymorphism and dyszoospermia. Ningxia Med J. 2017;39(2):97–100.Google Scholar
  9. 9.
    Liu SY, Zhang CJ, Peng HY, Sun H, Lin KQ, Huang XQ, et al. Strong association of SLC1A1 and DPF3 gene variants with idiopathic male infertility in Han Chinese. Asian J Androl. 2017;19(4):486–92.CrossRefGoogle Scholar
  10. 10.
    Zou S, Li Z, Wang Y, Chen T, Song P, Chen J, et al. Association study between polymorphisms of PRMT6, PEX10, SOX5, and nonobstructive azoospermia in the Han Chinese population. Biol Reprod. 2014;90(5):96.CrossRefGoogle Scholar
  11. 11.
    Munafò MR, Flint J. Meta-analysis of genetic association studies. Trends Genet. 2004;20(9):439–44.CrossRefGoogle Scholar
  12. 12.
    Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES Jr, Agarwal A. Critical appraisal of World Health Organization's new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology 2012;79(1):16–22.Google Scholar
  13. 13.
    Sedgwick P. Multiple significance tests: the Bonferroni correction. BMJ 2012;344.Google Scholar
  14. 14.
    Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127(9):820–6.CrossRefGoogle Scholar
  15. 15.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.Google Scholar
  16. 16.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefGoogle Scholar
  17. 17.
    El-Andaloussi N, Valovka T, Toueille M, Steinacher R, Focke F, Gehrig P, et al. Arginine methylation regulates DNA polymerase beta. Mol Cell. 2006;22(1):51–62.CrossRefGoogle Scholar
  18. 18.
    Sobol RW, Horton JK, Kuhn R, Gu H, Singhal RK, Prasad R, et al. Requirement of mammalian DNA polymerase-beta in base-excision repair. Nature. 1996;379(6561):183–6.CrossRefGoogle Scholar
  19. 19.
    Olsen AK, Bjørtuft H, Wiger R, Holme J, Seeberg E, Bjørås M, et al. Highly efficient base excision repair (BER) in human and rat male germ cells. Nucleic Acids Res. 2001;29(8):1781–90.CrossRefGoogle Scholar
  20. 20.
    Plug AW, Clairmont CA, Sapi E, Ashley T, Sweasy JB. Evidence for a role for DNA polymerase beta in mammalian meiosis. Proc Natl Acad Sci U S A. 1997;94(4):1327–31.CrossRefGoogle Scholar
  21. 21.
    Chen H, Liu Z, Huang X. Drosophila models of peroxisomal biogenesis disorder: peroxins are required for spermatogenesis and very-long-chain fatty acid metabolism. Hum Mol Genet. 2010;19(3):494–505.CrossRefGoogle Scholar
  22. 22.
    Takenaka K, Prasolava TK, Wang JC, Mortin-Toth SM, Khalouei S, Gan OI, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8(12):1313–23.CrossRefGoogle Scholar
  23. 23.
    Denny P, Swift S, Connor F, Ashworth A. An SRY-related gene expressed during spermatogenesis in the mouse encodes a sequence-specific DNA-binding protein. EMBO J. 1992;11(10):3705–12.CrossRefGoogle Scholar
  24. 24.
    Budde LM, Wu C, Tilman C, Douglas I, Ghosh S. Regulation of IkappaBbeta expression in testis. Mol Biol Cell. 2002;13(12):4179–94.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Reproductive Genetics, Center of Reproductive Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Family Planning Research Institute, Center of Reproductive Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Hospital Infection Control, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations