https://doi.org/10.18502/ijrm.v20i6.11446
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authors
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Elham Ghadirkhomi
Elham Ghadirkhomi
Department of Genetics, Faculty of Biological Science, North Tehran Branch, Islamic Azad University, Tehran, Iran.
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Seyed Abdolhamid Angaji
Seyed Abdolhamid Angaji
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
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Maryam Khosravi
Maryam Khosravi
Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
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Mohammad Reza Mashayekhi
Mohammad Reza Mashayekhi
Department of Genetics, Faculty of Biological Science, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Published Date
- Jul 6, 2022
Association study of novel single nucleotide polymorphisms of androgen receptor and estrogen receptor-α genes with male infertility in Northwest of Iran: A case-control study
Abstract
Background: Observational evidence on the association of novel single nucleotide polymorphisms (SNPs) of androgen receptor (AR) and estrogen receptor-α (ER-α) genes with odds of male infertility are rare. This is particularly relevant in the 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 the 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 - AR rs137852568, AR rs137852599 and AR rs137852563, and ER-α rs796065354 and ER-α rs104893956 - using amplification refractory mutation system methods.
Results: The 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 found on 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.
Key words: Male infertility, Androgen receptor, Estrogen receptor-α.
References
[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.
[4] O’Hara L, Smith LB. Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab 2015; 29: 595–605.
[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.
[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.
[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.
[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.
[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.
[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.
[14] Andrade DL, Viana MC, Esteves SC. Differential diagnosis of azoospermia in men with infertility. J Clin Med 2021; 10: 3144.
[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.
[16] Tournaye H, Krausz C, Oates RD. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol 2017; 5: 544–553.
[17] Mongan NP, Tadokoro-Cuccaro R, Bunch T, Hughes IA. Androgen insensitivity syndrome. Best Pract Res Clin Endocrinol Metab 2015; 29: 569–580.
[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.
[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.
[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.
[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.
[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.
[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.
[25] Dutta S, Sengupta P, Muhamad S. Male reproductive hormones and semen quality. Asian Pac J Reprod 2019; 8: 189–194.
[26] Abramovs N, Brass A, Tassabehji M. Hardy-weinberg equilibrium in the large scale genomic sequencing era. Front Genet 2020; 11: 210.