Volume 13, Issue 5 (7-2015)                   IJRM 2015, 13(5): 305-310 | Back to browse issues page

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1- Department of Genetics, Faculty of Sciences, Shahid Chamran University, Ahvaz, Iran
2- Department of Genetics, Faculty of Sciences, Shahid Chamran University, Ahvaz, Iran , srkhatami@yahoo.com
Abstract:   (2502 Views)
Background: Androgens play critical role in secondary sexual and male gonads differentiations such as spermatogenesis, via androgen receptor. The human androgen receptor (AR) encoding gene contains two regions with three nucleotide polymorphic repeats (CAG and GGN) in the first exon. Unlike the CAG repeats, the GGN has been less studied because of technical difficulties, so the functional role of these polymorphic repeats is still unclear.
Objective: The goal of this study was to investigate any relationship between GGN repeat length in the first exon of AR gene and idiopathic male infertility in southwest of Iran.
Materials and Methods: This is the first study on GGN repeat of AR gene in infertile male in Khuzestan, Iran. We used polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis to categorize GGN repeat lengths in 72 infertile and 72 fertile men. Afterwards we sequenced the PCR products to determine the exact length of GGN repeat in each category. Our samples included 36 azoospermic and 36 oligozoospermic men as cases and 72 fertile men as control group.
Results: We found that the numbers of repeats in the cases range from 18 to 25, while in the controls this range is from 20 to 28. The results showed a significant relation between the length of GGN repeat and fertility (p=0.015). The most frequent alleles were alleles with 24 and 25 repeats respectively in case and control groups. On the other hand no significant differences were found between Arab and non-Arab cases by considering GGN repeat lengths (p=0.234).
Conclusion: Due to our results, there is a significant association between the presence of allele with 24 repeats and susceptibility to male infertility. Therefore this polymorphism should be considered in future studies to clarify etiology of disorders related to androgen receptor activity.
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Type of Study: Original Article |

References
1. 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 2006; 27: 785-789. [DOI:10.2164/jandrol.106.000166]
2. Haqq CM, Donahoe PK. Regulation of sexual dimorphism in mammals. Physiol Rev 1998; 78: 1-33. [DOI:10.1152/physrev.1998.78.1.1]
3. Lundin KB, Giwercman A, Richthoff J, Abrahamsson PA and Giwercman YL. No association between mutations in the human androgen receptor GGN repeat and inter-sex conditions. Mol Hum Reprod 2003; 9: 375-379. [DOI:10.1093/molehr/gag048]
4. Lubahn DB, Joseph DR, Sullivan PM, Willard HF, French FS and Wilson EM. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988; 240: 327-330. [DOI:10.1126/science.3353727]
5. Ferlin A, Bartoloni L, Rizzo G, Roverato A, Garolla A and Foresta C. Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility. Mol Hum Reprod 2004; 10: 417-421. [DOI:10.1093/molehr/gah054]
6. Ruhayel Y, Lundin K, Giwercman Y, Hallden C, Willen M and Giwercman A. Androgen receptor gene GGN and CAG polymorphisms among severely oligozoospermic and azoospermic Swedish men. Hum Reprod 2004; 19: 2076-2083. [DOI:10.1093/humrep/deh349]
7. Lumbroso R, Beitel LK, Vasiliou DM, Trifiro MA and Pinsky L. Codon-usage variants in the polymorphic (GGN)n trinucleotide repeat of the human androgen receptor gene. Hum Genet 1997; 101: 43-46. [DOI:10.1007/s004390050583]
8. Chamberlain NL, Driver ED and Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994; 22: 3181-3186. [DOI:10.1093/nar/22.15.3181]
9. Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L and 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: 3777-3782. [DOI:10.1210/jc.82.11.3777]
10. McPhaul MJ. Molecular defects of the androgen receptor. J Steroid Biochem Mol Biol 1999; 69: 315-322. [DOI:10.1016/S0960-0760(99)00050-3]
11. Akinloye O, Gromoll J, Nieschlag E and Simoni M. Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men. J Endocrinol Invest 2009; 32: 797-804. [DOI:10.1007/BF03345748]
12. Castro-Nallar E, Bacallao K, Parada-Bustamante A, Lardone MC, Lopez PV, Madariaga M, et al. Androgen receptor gene CAG and GGN repeat polymorphisms in Chilean men with primary severe spermatogenic failure. J Androl 2010; 31: 552-529. [DOI:10.2164/jandrol.109.008821]
13. Parada-Bustamante A, Lardone MC, Valdevenito R, Ebensperger M, Lopez PV, Madariaga M, et al. Analysis of 6 single-nucleotide polymorphisms in the androgen receptor gene in Chilean patients with primary spermatogenic failure. J Androl 2012; 33: 88-95. [DOI:10.2164/jandrol.110.012195]
14. Han TT, Ran J, Ding XP, Li LJ, Zhang LY, Zhang YP, et al. Cytogenetic and molecular analysis of infertile Chinese men: karyotypic abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms in the androgen receptor gene. Genet Mol Res 2013; 12: 2215-2226. [DOI:10.4238/2013.July.8.3]
15. Correa-Cerro L, Wohr G, Haussler J, Berthon P, Drelon E, Mangin P, et al. (CAG)nCAA and GGN repeats in the human androgen receptor gene are not associated with prostate cancer in a French-German population. Eur J Hum Genet 1999; 7: 357-362. [DOI:10.1038/sj.ejhg.5200298]
16. Chen C, Lamharzi N, Weiss NS, Etzioni R, Dightman DA, Barnett M, et al. Androgen receptor polymorphisms and the incidence of prostate cancer. Cancer Epidemiol Biomarkers Prev 2002; 11: 1033-1040.
17. Hakimi JM, Schoenberg MP, Rondinelli RH, Piantadosi S and Barrack ER. Androgen receptor variants with short glutamine or glycine repeats may identify unique subpopulations of men with prostate cancer. Clin Cancer Res 1997; 3: 1599-1608.
18. Lange EM, Sarma AV, Ray A, Wang Y, Ho LA, Anderson SA, et al. The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men's Health Study. J Hum Genet 2008; 53: 220-226. [DOI:10.1007/s10038-007-0240-4]
19. Stanford JL, Just JJ, Gibbs M, Wicklund KG, Neal CL, Blumenstein BA, et al. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res 1997; 57: 1194-1198.
20.   20. Zeegers MP, Kiemeney LA, Nieder AM and Ostrer H. How strong is the association between CAG and GGN repeat length polymorphisms in the androgen receptor gene and prostate cancer risk? Cancer Epidemiol Biomarkers Prev 2004; 13: 1765-1771.
21. Aschim EL, Nordenskjold A, Giwercman A, Lundin KB, Ruhayel Y, Haugen TB, et al. Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. J Clin Endocrinol Metab 2004; 89: 5105-5109. [DOI:10.1210/jc.2004-0293]
22. Ferlin A, Garolla A, Bettella A, Bartoloni L, Vinanzi C, Roverato A, et al. Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism. Eur J Endocrinol 2005; 152: 419-425. [DOI:10.1530/eje.1.01860]
23. Radpour R, Rezaee M, Tavasoly A, Solati S and 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: 164-169. [DOI:10.2164/jandrol.106.000927]
24. Dunning AM, McBride S, Gregory J, Durocher F, Foster NA, Healey CS, et al. No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer. Carcinogenesis 1999; 20: 2131-2135. [DOI:10.1093/carcin/20.11.2131]
25. Kadouri L, Easton DF, Edwards S, Hubert A, Kote-Jarai Z, Glaser B, et al. CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers. Br J Cancer 2001; 85: 36-40. [DOI:10.1054/bjoc.2001.1777]
26. Suter NM, Malone KE, Daling JR, Doody DR and Ostrander EA. Androgen receptor (CAG)n and (GGC)n polymorphisms and breast cancer risk in a population-based case-control study of young women. Cancer Epidemiol Biomarkers Prev 2003; 12: 127-135.
27. Omrani MD. Androgen receptor gene trinucleotide repeats as a marker for tracing disease in afamily with intersex patients. Iran J Reprod Med 2006; 4: 4.
28. Chuan Z, Jie D, Hao X, Junhua B, Mengjing G, Liguo P, et al. Associations between androgen receptor CAG & GGN repeat polymorphism & recurrent spontaneous abortions in Chinese women. Indian J Med Res 2014; 139: 730-736.
29. Zirkin BR, Santulli R, Awoniyi CA and Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology 1989; 124: 3043-3049. [DOI:10.1210/endo-124-6-3043]
30. Brinkmann AO, Blok LJ, de Ruiter PE, Doesburg P, Steketee K, Berrevoets CA, et al. Mechanisms of androgen receptor activation and function. J Steroid Biochem Mol Biol 1999; 69: 307-713. [DOI:10.1016/S0960-0760(99)00049-7]
31. Jasinska A, Michlewski G, de Mezer M, Sobczak K, Kozlowski P, Napierala M, et al. Structures of trinucleotide repeats in human transcripts and their functional implications. Nucleic Acids Res 2003; 31: 5463-5468. [DOI:10.1093/nar/gkg767]
32. Yeap BB, Wilce JA and Leedman PJ. The androgen receptor mRNA. Bioessays 2004; 26: 672-682. [DOI:10.1002/bies.20051]

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