Volume 12, Issue 3 (4-2014)                   IJRM 2014, 12(3): 217-220 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Borhani N, Ghaffari Novin M, Manoochehri M, Rouzrokh M, Kazemi B, Koochaki A, et al . New single nucleotide variation in the promoter region of androgen receptor (AR) gene in hypospadic patients. IJRM. 2014; 12 (3) :217-220
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-515-en.html
1- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Department of Pediatric Surgery, Mofid Children's Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3- Department of Cell Biology and Anatomy, School of Medicine Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Department of Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran , davood_omrani@sbmu.ac.ir
Abstract:   (1369 Views)
Background: Hypospadias is one of the most common congenital abnormalities in the male which is characterized by altered development of urethra, foreskin and ventral surface of the penis. Androgen receptor gene plays a critical role in the development of the male genital system by mediating the androgens effects.
Objective: In present study, we looked for new variations in androgen receptor promoter and screened its exon 1 for five single nucleotide polymorphisms (SNP) in healthy and hypospadias Iranian men.
Materials and Methods: In our study, at first DNA was extracted from patients (n=100) and controls (n=100) blood samples. Desired fragments of promoter and exon 1 were amplified using polymerase chain reaction. The promoter region was sequenced for the new variation and exone 1 screened for five SNPs (rs139767835, rs78686797, rs62636528, rs62636529, rs145326748) using restriction fragment length polymorphism technique.
Results: The results showed a new single nucleotide variation (C→T) at -480 of two patients’ promoter region (2%). None of the mentioned SNPs were detected in patients and controls groups (0%).
Conclusion: This finding indicates that new single nucleotide polymorphism in androgen receptor promoter may have role in etiology of hypospadias and development of this anomaly.
Full-Text [PDF 143 kb]   (242 Downloads) |   |   Full-Text (HTML)  (128 Views)  
Type of Study: Original Article |

1. Carmichael SL, Shaw GM, Lammer EJ. Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence. Birth Defects Res A Clin Mol Teratol 2012; 94: 499-510. [DOI:10.1002/bdra.23021]
2. Carmichael SL, Shaw GM, Nelson V, Selvin S, Torfs CP, Curry CJ. Hypospadias in California: trends and descriptive epidemiology. Epidemiology 2003; 14: 701-706. [DOI:10.1097/01.ede.0000091603.43531.d0]
3. Muroya K, Sasagawa I, Suzuki Y, Nakada T, Ishii T, Ogata T. Hypospadias and the androgen receptor gene: mutation screening and CAG repeat length analysis. Mol Hum Reprod 2001; 7: 409-413. [DOI:10.1093/molehr/7.5.409]
4. Baskin LS. Hypospadias and urethral development. J Urol 2000; 163: 951-956. [DOI:10.1016/S0022-5347(05)67861-5]
5. Sasagawa I, Suzuki Y, Muroya K, Ogata T. Androgen receptor gene and male genital anomaly. Arch Androl 2002; 48: 461-466. [DOI:10.1080/0148501029009372]
6. Jaaskelainen J, Mongan NP, Harland S, Hughes IA. Five novel androgen receptor gene mutations associated with complete androgen insensitivity syndrome. Hum Mutat 2006; 27: 291. [DOI:10.1002/humu.9405]
7. Chamberlain NL, Driver ED, 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]
8. Svensson J, Snochowski M. Androgen receptor levels in preputial skin from boys with hypospadias. J Clin Endocrinol Metab 1979; 49: 340-345. [DOI:10.1210/jcem-49-3-340]
9. Keenan BS, McNeel RL, Gonzales ET. Abnormality of intracellular 5 alpha-dihydrotestosterone binding in simple hypospadias: studies on equilibrium steroid binding in sonicates of genital skin fibroblasts. Pediatr Res 1984; 18: 216-220. [DOI:10.1203/00006450-198402000-00020]
10. Simon S, Mueller SO. Human reporter gene assays: transcriptional activity of the androgen receptor is modulated by the cellular environment and promoter context. Toxicology 2006; 220: 90-103. [DOI:10.1016/j.tox.2005.12.002]
11. van der Zanden LF, van Rooij IA, Feitz WF, Franke B, Knoers NV, Roeleveld N. Aetiology of hypospadias: a systematic review of genes and environment. Hum Reprod Update 2012; 18: 260-283. [DOI:10.1093/humupd/dms002]
12. Waltering KK, Wallen MJ, Tammela TLJ, Vessella RL, Visakorpi T. Mutation screening of the androgen receptor promoter and untranslated regions in prostate cancer. Prostate 2006; 66: 1585-1591. [DOI:10.1002/pros.20387]
13. Ghadessy FJ, Liow SL, Yong EL. Mutations in the promoter region of the androgen receptor gene are not common in males with idiopathic infertility. Mol Hum Reprod 1999; 5: 287-290. [DOI:10.1093/molehr/5.3.287]
14. Cabral DF, Santos A, Ribeiro ML, Mesquita JC, Carvalho-Salles AB, Hackel C. Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene. Braz J Med Biol Res 2004; 37: 1789-1794. [DOI:10.1590/S0100-879X2004001200004]
15. 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: 164-169. [DOI:10.2164/jandrol.106.000927]
16. Allera A, Herbst MA, Griffin JE, Wilson JD, Schweikert HU, McPhaul MJ. Mutations of the androgen receptor coding sequence are infrequent in patients with isolated hypospadias. J Clin Endocrinol Metab 1995; 80: 2697-2699. [DOI:10.1210/jc.80.9.2697]
17. Sutherland RW, Wiener JS, Hicks JP, Marcelli M, Gonzales ET Jr, Roth DR, et al. Androgen receptor gene mutations are rarely associated with isolated penile hypospadias. J Urol 1996; 156: 828-831. [DOI:10.1016/S0022-5347(01)65830-0]
18. Adamovic T, Thai HT, Lieden A, Nordenskjold A. Association of a tagging single nucleotide polymorphism in the androgen receptor gene region with susceptibility to severe hypospadias in a caucasian population. Sex Dev 2013; 7: 173-179. [DOI:10.1159/000348882]
19. Adamovic T, Nordenskjold A. The CAG repeat polymorphism in the androgen receptor gene modifies the risk for hypospadias in Caucasians. BMC Med Genet 2012; 13: 109. [DOI:10.1186/1471-2350-13-109]
20. Parada-Bustamante A, Lardone MC, Madariaga M, Johnson MC, Codner E, Cassorla F, et al. Androgen receptor CAG and GGN polymorphisms in boys with isolated hypospadias. J Pediatr Endocrinol Metab 2012; 25: 157-162. [DOI:10.1515/jpem.2011.379]

Send email to the article author

© 2021 CC BY-NC 4.0 | International Journal of Reproductive BioMedicine

Designed & Developed by : Yektaweb