Volume 20, Issue 6 (June 2022)                   IJRM 2022, 20(6): 501-510 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Ghadirkhomi E, Angaji S A, Khosravi M, Mashayekhi M R. Association study of novel single nucleotide polymorphisms of androgen receptor and estrogen receptor-α genes with male infertility in North West of Iran: a case- control study. IJRM 2022; 20 (6) :501-510
URL: http://ijrm.ir/article-1-2184-en.html
Association study of novel single nucleotide polymorphisms of androgen receptor and estrogen receptor-α genes with male infertility in North West of Iran: a case- control study
Elham Ghadirkhomi1 , Seyed Abdolhamid Angaji * 2, Maryam Khosravi3 , Mohammad Reza Mashayekhi4
1- Department of Genetics, Faculty of Biological Science, North Tehran Branch, Islamic Azad University, Tehran, Iran.
2- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. , vo83ge@yahoo.com
3- Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
4- Department of Genetics, Faculty of Biological Science, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Abstract:   (1192 Views)
Background: Observational evidence on the association of novel single nucleotide polymorphism (SNPs) of androgen receptor (AR) and estrogen receptor-α (ER-α) genes with odds of male infertility are rare. This is particularly relevant in Iranian population where male infertility is relatively high.
Objective: This study was designed to investigate the relationship between different SNPs of these genes and male infertility among Iranian population.
Materials and Methods: The present project was a population-based, case-control study conducted on 120 idiopathic azoospermia or severe oligospermia infertile cases alongside 120 age-matched subjects enrolled as controls. Overall, 3 variants from the AR gene and 2 variants from ER-α were genotyped - ARrs137852568, ARrs137852599, and AR rs137852563 and ER-α rs796065354, and ER-αrs104893956- using amplification refractory mutation system methods.
Results: Obtained results indicated a significant association between AR rs1378525568 TT genotype as well as AR rs137852599 C allele with odds of male infertility (OR: 0.433, CI: 0.197-0.951 and OR: 0.545, CI: 0.304-0.978, respectively). Other variants of AR were not related to male infertility. A significant association was noted between predisposition polymorphism ER-α rs796065354 genotypes with male infertility. This significant association was not seen between ER-α rs104893956 and the risk of idiopathic azoospermia or severe oligospermia. Heterozygote overdominance was also observed in ESR rs796065354 but not in the other variants studied.
Conclusion: Pieces of evidence were foundon the association of novel polymorphisms of AR and ER-α with male infertility among the Iranian population. However, larger studies are warranted to confirm our findings.
Keywords: Male infertility, Androgen receptor, Estrogen receptor-α.
Full-Text [PDF 287 kb]   (828 Downloads) |   |   Full-Text (HTML)  (280 Views)  
Type of Study: Original Article | Subject: Reproductive Urology
References
1. Parsanezhad ME, Namavar Jahromi B, Zare N, Keramati P, Khalili A, Parsa-Nezhad M. Epidemiology and etiology of infertility in Iran: Systematic review and meta-analysis. J Womens Health, Issues Care, 2013; 2: 6. [DOI:10.4172/2325-9795.1000121]
2. Akhondi MM, Ranjbar F, Shirzad M, Behjati Ardakani Z, Kamali K, Mohammad K. Practical difficulties in estimating the prevalence of primary infertility in Iran. Int J Fertil Steril 2019; 13: 113-117.
3. Sen S, Dixit A, Thakur Ch, Gokral J, Hinduja I, Zaveri K, et al. Association of progesterone receptor gene polymorphism with male infertility and clinical outcome of ICSI. J Assist Reprodu Genet 2013; 30: 1133-1139. [DOI:10.1007/s10815-013-0074-2] [PMID] [PMCID]
4. O'Hara L, Smith LB. Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab 2015; 29: 595-605. [DOI:10.1016/j.beem.2015.04.006] [PMID]
5. O'Hara L, Smith LB. The genetics of androgen receptor signalling in male fertility. In: Voght PH. Genetics of human infertility. New Yok: Karger Publishers; 2017: 86-100. [DOI:10.1159/000477280]
6. 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 Endocrinol Metab 2007; 92: 4319-4326. [DOI:10.1210/jc.2007-1110] [PMID]
7. Xiao F, Lan A, Lin Zh, Song J, Zhang Y, Li J, et al. Impact of CAG repeat length in the androgen receptor gene on male infertility: A meta-analysis. Reprod Biomed Online 2016; 33: 39-49. [DOI:10.1016/j.rbmo.2016.03.012] [PMID]
8. Pan B, Li R, Chen Y, Tang Q, Wu W, Chen L, et al. Genetic association between androgen receptor gene CAG repeat length polymorphism and male infertility: A meta-analysis. Medicine 2016; 95: e2878. [DOI:10.1097/MD.0000000000002878] [PMID] [PMCID]
9. Mobasseri N, Babaei F, Karimian M, Nikzad H. Androgen receptor (AR)-CAG trinucleotide repeat length and idiopathic male infertility: A case-control trial and a meta-analysis. EXCLI J 2018; 17: 1167-1179.
10. Cerván-Martín M, Castilla JA, Palomino-Morales RJ, Carmona FD. Genetic landscape of nonobstructive azoospermia and new perspectives for the clinic. J Clin Med 2020; 9: 300. [DOI:10.3390/jcm9020300] [PMID] [PMCID]
11. Rivera-Diaz PA, Patricia Ortiz C, Ricardo Delgado D. The crucial role of estrogen/androgen hormones and their receptors in male infertility risk. Central Asian J Med Pharm Sci Innovat 2021; 1: 35-43.
12. Moghadam M, Khatami SR, Galehdari H. Association of androgen receptor GGN repeat length polymorphism and male infertility in Khuzestan, Iran. Iran J Reprod Med 2015; 13: 305-310.
13. Nemati H, Sadeghi M, Nazeri M, Mohammadi M. Evaluation of the association between polymorphisms of PRM1 and PRM2 and the risk of male infertility: A systematic review, meta-analysis, and meta-regression. Sci Rep 2020; 10: 17228. [DOI:10.1038/s41598-020-74233-3] [PMID] [PMCID]
14. Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med 2021; 10: 3144. [DOI:10.3390/jcm10143144] [PMID] [PMCID]
15. Zalata A, Abdalla HA, El‐Bayoumy Y, Mostafa T. Oestrogen receptor alpha gene polymorphisms relationship with semen variables in infertile men. Andrologia 2014; 46: 618-624. [DOI:10.1111/and.12123] [PMID]
16. Tournaye H, Krausz C, Oates RD. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol 2017; 5: 544-553. https://doi.org/10.1016/S2213-8587(16)30043-2 [DOI:10.1016/S2213-8587(16)30040-7]
17. Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab 2015; 29: 569-580. [DOI:10.1016/j.beem.2015.04.005] [PMID]
18. Ferlin A, Bartoloni L, Rizzo G, Roverato A, Garolla A, 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] [PMID]
19. Giagulli VA, Carbone MD, De Pergola G, Guastamacchia E, Resta F, Licchelli B, et al. Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility? J Assist Reprod Genet 2014; 31: 689-697. [DOI:10.1007/s10815-014-0221-4] [PMID] [PMCID]
20. Demirkan S, Sayın DB, Gündüz Ö. CAG polymorphism in the androgen receptor gene in women may be associated with nodulocystic acne. Postepy Dermatol Alergol 2019; 36: 173-176. [DOI:10.5114/ada.2019.84592] [PMID] [PMCID]
21. Guido C, Perrotta I, Panza S, Middea E, Avena P, Santoro M, et al. Human sperm physiology: Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) influence sperm metabolism and may be involved in the pathophysiology of varicocele‐associated male infertility. J Cell Physiol 2011; 226: 3403-3412. [DOI:10.1002/jcp.22703] [PMID]
22. Fernández R, Delgado-Zayas E, Ramírez K, Cortés-Cortés J, Gómez-Gil E, Esteva E, et al. Analysis of four polymorphisms located at the promoter of the estrogen receptor Alpha ESR1 gene in a population with gender incongruence. Sex Med 2020; 8: 490-500. [DOI:10.1016/j.esxm.2020.04.002] [PMID] [PMCID]
23. Liaqat S, Hasnain Sh, Muzammil S, Hayat S. Polymorphism analysis in estrogen receptors alpha and beta genes and their association with infertile population in Pakistan. EXCLIJ 2015; 14: 1085.
24. Lazaros LA, Xita NV, Kaponis AI, Zikopoulos KA, Plachouras NI, Georgiou IA. Estrogen receptor α and β polymorphisms are associated with semen quality. J Androl 2010; 31: 291-298. [DOI:10.2164/jandrol.109.007542] [PMID]
25. Dutta S, Sengupta P, Muhamad S. Male reproductive hormones and semen quality. Asian Pac J Reprod 2019; 8: 189-194. [DOI:10.4103/2305-0500.268132]
26. Abramovs N, Brass A, Tassabehji M. Hardy-weinberg equilibrium in the large scale genomic sequencing era. Front Genet 2020; 11: 210. [DOI:10.3389/fgene.2020.00210] [PMID] [PMCID]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb