Journal of Endocrinological Investigation

, Volume 32, Issue 10, pp 797–804 | Cite as

Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men

  • O. Akinloye
  • J. Gromoll
  • E. Nieschlag
  • M. Simoni
Original Articles


The human androgen receptor gene (AR) is an important regulator of male sexual development including spermatogenesis. Exon 1 of this gene encodes the N terminal domain, which controls transcriptional activity of the receptor and the two polymorphic repeats CAG and GGN. Many studies have reported association of the expanded CAG repeat length with male infertility, although this is still controversial. The GGN repeat, in contrast, has been less thoroughly studied. Thus far, only scanty studies have been reported from African populations and none from Nigeria. Therefore, we have investigated the possible association between AR polymorphism repeats length (CAG and GGN) and reduced spermatogenesis in infertile Nigerian men (no.=60) consisting of 20 non-obstructive azoospermic and 40 oligozoospermic subjects compared with controls with normozoospermia and proven evidence of fertility (no.=38). In addition, 48 volunteers with normal spermatogenesis were recruited from a German population. CAG and GGN repeats length were determined by fragment length analysis using GeneScan. The CAG and GGN repeats length of infertile compared to fertile populations were not significantly different (p>0.05). We found a unique AR GGN allele distribution with 20–23 GGN repeats predominant in the Nigerian study population. Our results show that CAG and GGN repeats polymorphisms are not a critical index of male infertility. While we do not find a relationship with CAG and GGN repeats haplotypes and male infertility, we report for the first time a unique and wider distribution of the GGN allele in the Nigerian population which is significantly different from the Caucasian population. The functional relevance of this variance to male fertility warrants in-depth elucidation.


Androgen receptor CAG GGN male infertility Nigeria polymorphisms 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Okonofua F. New reproductive technologies and infertility treatment in Africa. Afr J Reprod Health 2003, 7: 7–11.Google Scholar
  2. 2.
    Chukudebelu WO. The male factor in infertility — Nigerian experience. Int J Fertil 1978, 23: 238–9.PubMedGoogle Scholar
  3. 3.
    Esimai OA, Orji EO, Lasisi AR. Male contribution to infertility in IleIfe, Nigeria. Niger J Med 2002, 11: 70–2.PubMedGoogle Scholar
  4. 4.
    Samli H, Samli MM, SolakTM, Imirzalioglu N. Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl 2006, 52: 263–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Foresta C, Ferlin A, Gianaroli L, Dalla Piccola B. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet 2002, 10: 303–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet 2004, 364: 273–83.PubMedCrossRefGoogle Scholar
  7. 7.
    Simoni M, Gromoll J, Dworniczak B, et al. Screening for deletions of the Y chromosome involving the DAZ (deleted in azoospermia) gene in azoospermia and severe oligospermia. Fertil Steril 1997, 67: 542–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Page DC, Silber S, Brown LG. Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum Reprod 1999, 14: 1722–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Maurer B, Gromoll J, Simoni M, Nieschlag E. Prevalence of Y chromosome microdeletions in infertile men who consulted a tertiary care medical centre: the Münster experience. Andrologia 2001, 33: 27–33.PubMedCrossRefGoogle Scholar
  10. 10.
    Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alteration of spermatogenesis. Endocr Rev 2001, 22: 226–39.PubMedGoogle Scholar
  11. 11.
    Krausz C, Fellous M. Chromosome Y and infertility in men. Ann Endocrinol (Paris) 2003, 64: 403–12.Google Scholar
  12. 12.
    Vogt PH. Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online 2005, 10: 81–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Hucklenbroich K, Gromoll J, Heinrich M, Hohoff C, Nieschlag E, Simoni M. Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod 2005, 20: 191–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Fernando L, Gromoll J, Weerasooriya TR, Nieschlag, Simoni M. Y-chromosomal microdeletions and partial deletions of the Azoospermia Factor c (AZFc) region in normozoospermic, severe oligozoospermic and azoospermic men in Sri Lanka. Asian J Androl 2006, 8: 39–44.PubMedCrossRefGoogle Scholar
  15. 15.
    Gao T, Marcelli M, McPhaul MJ. Transcriptional activation and transient expression of the human androgen receptor. J Steroid Biochem Mol Biol 1996, 59: 9–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Asatiani K, von Eckardstein S, Simoni M, Gromoll J, Nieschlag E. CAG repeat length in the androgen receptor gene affects the risk of male infertility. Int J Androl 2003, 26: 255–61.PubMedCrossRefGoogle Scholar
  17. 17.
    von Eckardstein S, Syska A, Gromoll J, Kamischke A, Simoni M, Nieschlag E. Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men. J Clin Endocrinol Metab 2001, 86: 2585–90.Google Scholar
  18. 18.
    Kittles R A, Young D, Weinrich S, Hudson J, Argyropoulos G, Ukoli F, Adams-Campbell Land Dunston GM. Extent of linkage equilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk. Hum Genet 2001, 109: 253–61.PubMedCrossRefGoogle Scholar
  19. 19.
    Lundin KB, Giwercman YL, Rylander L, Hagmar L, Giwercman A. Androgen receptor gene GGN repeats length and reproductive characteristics in young Swedish men. Eur J Endocrinol 2006, 155: 347–54.PubMedCrossRefGoogle Scholar
  20. 20.
    Rajender S Rajani V, Gupta NJ, Chakravarty B, Singh L, Thangaraj K. No association of androgen receptor GGN repeat length polymorphism with infertility in Indian men. J Androl 27: 785–9.Google Scholar
  21. 21.
    Ferlin A Bartoloni L Rizzo G Roverato A Garolla A, Foresta C. Androgen receptor gene CAG and GGN repeats lengths in idiopathic male infertility. Mol Hum Reprod 2004, 10: 417–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Ruhayel Y, Lundin K, Giwercman Y, Halldén C, Willén M, Giwercman A. Androgen receptor gene GGN and CAG polymorphisms among severely oligozoospermic and azoospermic Swedish men. Hum Reprod 2004, 19: 2076–83.PubMedCrossRefGoogle Scholar
  23. 23.
    Saare M, Belousova A, Punab M, et al. Androgen receptor gene haplotype is associated with male infertility. Int J Androl 2008, 31: 395–402.PubMedCrossRefGoogle Scholar
  24. 24.
    Tüttelmann F, Luetjens CM, Nieschlag E. Optimising workflow in andrology: a new electronic patient record and database. Asian J Androl 2006, 8: 235–41.PubMedCrossRefGoogle Scholar
  25. 25.
    World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interactions. 4th ed. Cambridge/New York: Cambridge University Press, 1999.Google Scholar
  26. 26.
    Dadze S, Wieland C, Jakubiczka S, Funke E, Schröder E. The size of CAG repeats in exon 1 of the androgen receptor gene expression shows no significant relationship to impaired spermatogenesis in an infertile Caucasoid sample of German origin. Mol Hum Reprod 2000, 6: 207–14.PubMedCrossRefGoogle Scholar
  27. 27.
    Dhillon VS, Husain SA. Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men. Int J Androl 2003, 26: 286–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Thangaraj K, Joshi M, Reddy AG, Gupta NJ, Chakravarty B, Singh L. CAG repeat expansion in the androgen receptor gene is not associated with infertility in Indian population. J Androl 2002, 23: 815–8.PubMedGoogle Scholar
  29. 29.
    Hadjkacem L, Hadj-Kacem H, Boulila A, Bahloul A, Ayadi H, Ammar-Keskes L. Androgen receptor gene CAG repeats length in fertile and infertile Tunisian men. Ann Genet 2004, 47: 217–24.PubMedCrossRefGoogle Scholar
  30. 30.
    Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrin Metab 2007, 92: 4319–26.CrossRefGoogle Scholar
  31. 31.
    Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 1997, 82: 3777–82.PubMedGoogle Scholar
  32. 32.
    Aschim EL, Nordenskjöld A, Giwercman A, et al. Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. J Clin Endocr Metab 2004, 89: 5105–09.PubMedCrossRefGoogle Scholar
  33. 33.
    Radpour R, Rezaee M, Tavasoly A, Solati S, Saleki A. Association of long polyglycine tracts (GGN repeats) in exon 1 of the androgen receptor gene with cryptorchidism and penile hypospadias in Iranian patients. J Androl 2007, 28: 164–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Hillmer AM, Hanneken S, Ritzmann S, et al. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet 2005, 77: 140–8.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Irvine RA, Yu MC, Ross RK, Coetzee GA. The CAG and GGC microsatellites of the androgen receptor gene is in linkage disequilibrium in men with prostate cancer. Cancer Res 1994, 55: 1937–40.Google Scholar
  36. 36.
    Sartor O, Zheng Q, Eastham JA. Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer. Urology 1999, 53: 378–80.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2009

Authors and Affiliations

  • O. Akinloye
    • 1
    • 2
  • J. Gromoll
    • 1
  • E. Nieschlag
    • 1
  • M. Simoni
    • 1
  1. 1.Institute of Reproductive Medicine of the UniversityMünsterGermany
  2. 2.Department of Chemical Pathology, College of Health SciencesLadoke Akintola University of TechnologyOsogboNigeria

Personalised recommendations