DOI QR코드

DOI QR Code

Genetic association study of a single nucleotide polymorphism of kallikrein-related peptidase 2 with male infertility

  • Lee, Sun-Hee (Department of Biomedical Science, College of Life Science, CHA University) ;
  • Lee, Su-Man (Department of Biomedical Science, College of Life Science, CHA University)
  • Received : 2010.11.15
  • Accepted : 2011.01.01
  • Published : 2011.03.02

Abstract

Objective: To investigate a kallikrein-related peptidase 2 (KLK2) single nucleotide polymorphism (SNP) in relation to male infertility because of its role in semen processing. We investigated the genetic association of the KLK2+255G>A genotype with male infertility. Methods: We genotyped the SNP site located in intron 1 (+255G>A, rs2664155) of KLK2 from 218 men with male infertility (cases) and 220 fertile males (controls). Pyrosequencing analysis was performed for the genotyping. Results: The SNP of the KLK2 gene had a statistically significant association with male infertility (p<0.05). The odds ratio for the minor allele (+255A) in the pooled sample was 0.47 (95% confidence intervals, 0.26-0.85) for rs2664155. Conclusion: The relationship of KLK2 SNP to male infertility is statistically significant, especially within the non-azoospermia group. Further study is needed to understand the mechanisms associated with male infertility.

Keywords

References

  1. Lynch ED, Lee MK, Morrow JE, Welcsh PL, León PE, King MC. Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 1997;278: 1315-8. https://doi.org/10.1126/science.278.5341.1315
  2. García-Herrero S, Meseguer M, Martínez-Conejero JA, Remohí J, Pellicer A, Garrido N. The transcriptome of spermatozoa used in homologous intrauterine insemination varies considerably between samples that achieve pregnancy and those that do not. Fertil Steril 2010;94:1360-73.
  3. Emami N, Deperthes D, Malm J, Diamandis EP. Major role of human KLK14 in seminal clot liquefaction. J Biol Chem 2008;283: 19561-9. https://doi.org/10.1074/jbc.M801194200
  4. Kamischke A, Nieschlag E. Conventional treatments of male infertility in the age of evidence-based andrology. Hum Reprod 1998;13 Suppl 1:62-75. https://doi.org/10.1093/humrep/13.suppl_1.62
  5. Nam RK, Zhang WW, Klotz LH, Trachtenberg J, Jewett MA, Sweet J, et al. Variants of the hK2 protein gene (KLK2) are associated with serum hK2 levels and predict the presence of prostate cancer at biopsy. Clin Cancer Res 2006;12:6452-8. https://doi.org/10.1158/1078-0432.CCR-06-1485
  6. Lovgren J, Rajakoski K, Karp M, Lundwall a, Lilja H. Activation of the zymogen form of prostate-specific antigen by human glandular kallikrein 2. Biochem Biophys Res Commun 1997;238:549- 55. https://doi.org/10.1006/bbrc.1997.7333
  7. Gerhar I, Wallis E. Individualized homeopathic therapy for male infertility. Homeopathy 2002;91:133-44. https://doi.org/10.1054/homp.2002.0024
  8. Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001;22:184-204. https://doi.org/10.1210/er.22.2.184
  9. Lee J, Park HS, Kim HH, Yun YJ, Lee DR, Lee S. Functional polymorphism in H2BFWT-5'UTR is associated with susceptibility to male infertility. J Cell Mol Med 2009;13:1942-51. https://doi.org/10.1111/j.1582-4934.2009.00830.x
  10. World Health Organisation. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999.
  11. Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics 2006;22: 1928-9. https://doi.org/10.1093/bioinformatics/btl268
  12. Pakkala M, Hekim C, Soininen P, Leinonen J, Koistinen H, Weisell J, et al. Activity and stability of human kallikrein-2-specific linear and cyclic peptide inhibitors. J Pept Sci 2007;13:348-53. https://doi.org/10.1002/psc.849
  13. Lintula S, Stenman J, Bjartell A, Nordling S, Stenman UH. Relative concentrations of hK2/PSA mRNA in benign and malignant prostatic tissue. Prostate 2005;63:324-9. https://doi.org/10.1002/pros.20194
  14. Alapont Alacreu JM, Navarro Rosales S, Budia Alba A, Espana Furio F, Morera Martinez F, Jimenez Cruz JF. PSA and hK2 in the diagnosis of prostate cancer. Actas Urol Esp 2008;32:575-88. https://doi.org/10.1016/S0210-4806(08)73891-9
  15. Lundwall A, Brattsand M. Kallikrein-related peptidases. Cell Mol Life Sci 2008;65:2019-38. https://doi.org/10.1007/s00018-008-8024-3
  16. David A, Mabjeesh N, Azar I, Biton S, Engel S, Bernstein J, et al. Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins. J Biol Chem 2002;277:18084-90. https://doi.org/10.1074/jbc.M102285200
  17. Andrade-Rocha FT. Unusual presentation of seminal vesiculitis in an infertile man. Can J Urol 2007;14:3750-2.
  18. Emami N, Scorilas A, Soosaipillai A, Earle T, Mullen B, Diamandis EP. Association between kallikrein-related peptidases (KLKs) and macroscopic indicators of semen analysis: their relation to sperm motility. Biol Chem 2009;390:921-9.