Association between genetic variants in hsa-miR-27a and hsa-miR-146a gene and male infertility
Abstract
Background: miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and diseases of the reproductive system. The aim of this study was to investigate the association between the two functional genetic variants in the hsa-miR-27a (rs2910164) and hsa-miR-146a gene (rs895819) and male infertility in North Macedonian population, as well as to test their association with the values of major seminal parameters.
Methods: The case group included in this study comprised 158 men initially diagnosed with idiopathic male infertility. The control group included 126 age-matched healthy male volunteers who fathered at least one child.
Results: We report for the first time the association of rs2910164 minor allele C with the increased susceptibility to asthenoteratozoospermia. Additionally, our results indicating the association of allele C with low sperm vitality are a novel finding. We did not demonstrate the association between genetic variant rs895819 and the risk of different types of male infertility. Still, the number of participants with CC genotype in subjects diagnosed with asthenoteratozoospermia was null, while in controls it reached 7.2%. We further detected the rs895819 genotype-dependent difference in rapid progressive sperm motility.
Conclusions: The association of rs2910164 and rs895819 with idiopathic male infertility in general is unlikely. However, both of these variants show association with certain types of male infertility and with sperm abnormalities, which need to be confirmed in later studies in different ethnic groups.
References
2. Salas-Huetos A, James ER, Aston KI, Carrell DT, Jenkins TG, Yeste M. The role of miRNAs in male human reproduction: a systematic review. Andrology 2020; 8: 7-26.
3. Khawar MB, Mehmood R, Roohi N. MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers. Bosn J Basic Med Sci 2019; 19: 31-42.
4. Barbu MG, Thompson DC, Suciu N, Voinea SC, Cretoiu D, Predescu DV. The Roles of MicroRNAs in Male Infertility. Int J Mol Sci 2021; 22: 2910.
5. Nikolić ZZ, Savić Pavićević DLj, Vukotić VD, Tomović SM, Cerović SJ, Filipović N, et al. Association between genetic variant in hsa-miR-146a gene and prostate cancer progression: evidence from Serbian population. Cancer Causes Control 2014; 25: 1571-5.
6. Bi W, Li J, Xiong M, Pan B, Zhang Z, Nasifu L, et al. The diagnostic and prognostic role of miR-27a in cancer. Pathol Res Pract 2023; 247: 154544.
7. Norioun H, Motovali-Bashi M, Javadirad SM. Hsa-miR-27a-3p overexpression in men with nonobstructive azoospermia: A case-control study. Int J Reprod Biomed 2020; 18: 961-8.
8. Shi D, Li P, Ma L, Zhong D, Chu H, Yan F, et al. A genetic variant in pre-miR-27a is associated with a reduced renal cell cancer risk in a Chinese population. PLoS One 2012; 7: e46566.
9. Rajovski S, Vučić N, Karanović J, Matijašević S, Savić-Pavićević D, Dobrijević Z, et al. Association of PRMT6, PEX10 and SOX5 genetic variants with idiopathic male infertility: Evidence from North Macedonian population and an updated meta-analysis. Genetika 2023; 55: 355-72.
10. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 2015; 8: 191-6.
11. Krausz C, Escamilla AR, Chianese C. Genetics of male infertility: from research to clinic. Reproduction. 2015; 150: R159-74.
12. Klees C, Alexandri C, Demeestere I, Lybaert P. The Role of microRNA in Spermatogenesis: Is There a Place for Fertility Preservation Innovation? Int J Mol Sci 2023; 25: 460.
13. Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 2010; 10: 389-402.
14. Nikolić ZZ, Savić Pavićević DL, Vučic NL, Romac SP, Brajušković GN. Association between a Genetic Variant in the hsa-miR-146a Gene and Cancer Risk: An Updated Meta-Analysis. Public Health Genomics 2015; 18: 283-98.
15. Dai J, Chen Y, Gong Y, Gu D, Chen J. Association of microRNA-27a rs895819 polymorphism with the risk of cancer: An updated meta-analysis. Gene 2020; 728: 144185.
16. Li G, Liu B, Jiang Q, Zhang J, Xin S, Xu K. The association of two common polymorphisms in miRNAs with diabetes mellitus: A meta-analysis. Medicine (Baltimore) 2019; 98: e17414.
17. Wang X, Xing Y, Wang Y, Du Z, Zhang C, Gao J. Association of microRNA gene polymorphisms with recurrent spontaneous abortion: An updated meta‑analysis. Exp Ther Med 2023; 25: 179.
18. Zhang J, Tan H, Cao Q, Su G, Yang P. Meta-Analysis of miRNA Variants Associated with Susceptibility to Autoimmune Disease. Dis Markers 2021; 2021: 9978460.
19. Abu-Halima M, Galata V, Backes C, Keller A, Hammadeh M, Meese E. MicroRNA signature in spermatozoa and seminal plasma of proven fertile men and in testicular tissue of men with obstructive azoospermia. Andrologia 2020; 52: e13503.
20. Zhou JH, Zhou QZ, Yang JK, Lyu XM, Bian J, Guo WB, et al. MicroRNA-27a-mediated repression of cysteine-rich secretory protein 2 translation in asthenoteratozoospermic patients. Asian J Androl 2017; 19: 591-5. Erratum in: Asian J Androl 2023; 25:758.
21. Robertson SA, Zhang B, Chan H, Sharkey DJ, Barry SC, Fullston T, et al. MicroRNA regulation of immune events at conception. Mol Reprod Dev 2017; 84: 914-25.
22. Zhao Y, Dong D, Reece EA, Wang AR, Yang P. Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy. Am J Obstet Gynecol 2018; 218: 136.e1-136.e10.
23. Fletcher CE, Dart DA, Sita-Lumsden A, Cheng H, Rennie PS, Bevan CL. Androgen-regulated processing of the oncomir miR-27a, which targets Prohibitin in prostate cancer. Hum Mol Genet 2012; 21: 3112-27.
24. Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, et al. A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 2010; 70: 467-72.
25. Sun Q, Gu H, Zeng Y, Xia Y, Wang Y, Jing Y, et al. Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression. Cancer Sci 2010; 101: 2241-7.
26. Nikolić Z, Savić Pavićević D, Vučić N, Cidilko S, Filipović N, Cerović S, et al Assessment of association between genetic variants in microRNA genes hsa-miR-499, hsa-miR-196a2 and hsa-miR-27a and prostate cancer risk in Serbian population. Exp Mol Pathol 2015; 99: 145-50.
27. Tunçdemir M, Yenmiş G, Tombultürk K, Arkan H, Soydaş T, Burak Tek R, et al. NFKB1 rs28362491 and pre-miRNA-146a rs2910164 SNPs on E-Cadherin expression in case of idiopathic oligospermia: A case-control study. Int J Reprod Biomed 2018; 16: 247-54.
28. Lu J, Gu H, Tang Q, Wu W, Yuan B, Guo D, et al. Common SNP in hsa-miR-196a-2 increases hsa-miR-196a-5p expression and predisposes to idiopathic male infertility in Chinese Han population. Sci Rep 2016; 6: 19825.
29. Vučić N, Nikolić Z, Savić Pavićević D, Kanazir S, Vukotić V, Romac S, et al. Assessment of possible association between genetic variant rs895819 in miR-27a gene and infertility in males diagnosed with non-obstructive azoospermia (NOA) from Serbian population [abstract]. EAU 10th South Eastern European Meeting (SEEM); 2014 Oct 24-26; Belgrade, Serbia. Eur Urol Suppl 2014; 13: e1475.
Copyright (c) 2024 Zorana Dobrijević, Srećko Rajovski, Suzana Matijašević Joković, Nikoleta Milanović, Nemanja Radovanović, Miloš Brkušanin, Dušanka Savić-Pavićević, Goran Brajušković
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