Study on Bosnian unexplained abortions (BUNA) and the introgression from Neanderthal Man, rs1042838 of PGR gene

Grażyna Adler, Mateusz Adler, Izabela Uzar, Emir Mahmutbegović

Abstract


Introduction: In European couples infertility varies 5–24%. The progesterone receptor (PGR) encoded by the PGR gene plays a key role in many reproductive pathways. In our study, for the first time among European populations, the potential association of PGR rs1042838 with spontaneous abortions (SA), was investigated.
Materials and methods: The TaqMan SNP assay was used in a group of 154 women with SA and 154 controls – mothers with at least 1 live-born child for genotyping the rs1042838 of PGR gene.
Results: The prevalence of genotypes GG, GT, TT in women with and without SAs were: 72.8%, 22.7%, 4.5% and 61.0%, 34.4% and 4.6%, respectively (p = 0.080).
Conclusions: Due to the fact that in some populations rs1042838 is rare, its confirmation as a genetic marker of SA requires further studies in larger groups and different populations.

Keywords


pregnancy loss; PGR gene; single nucleotide polymorphism

Full Text:

PDF

References


Elhussein OG, Ahmed MA, Suliman SO, Yahya LI, Adam I. Epidemiology of infertility and characteristics of infertile couples requesting assisted reproduction in a low-resource setting in Africa. Sudan. Fertil Res Pract 2019;5:7. doi: 10.1186/s40738-019-0060-1.

Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M. Stephenson MD, Fisher J, et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet 2021;397(10285):1658-67. doi: 10.1016/S0140-6736(21)00682-6.

Ventura SJ, Curtin SC, Abma JC, Henshaw SK. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990–2008. National Vital Statistic Reports 2012;60(7):1-21.

Blackmore ER, Cote-Arsenault D, Tang W, Glover V, Evans J, Golding J, et al. Previous prenatal loss as a predictor of perinatal depression and anxiety. Br J Psychiatry 2011;198(5):373-8. doi: 10.1192/bjp.bp.110.083105.

Giannandrea SA, Cerulli C, Anson E, Chaudron LH. Increased risk for postpartum psychiatric disorders among women with past pregnancy loss. J Womens Health (Larchmt) 2013;22(9):760-8. doi: 10.1089/jwh.2012.4011.

Farren J, Jalmbrant M, Falconieri N, Mitchell-Jones N, Bobdiwala S, Al-Memar M, et al. Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study. Am J Obstet Gynecol 2020;222(4):367.e1-367.e22. doi: 10.1016/j.ajog.2019.10.102.

Li R, Wang X, Huang Z, Balaji J, Kim TH, Wang T, et al. The role of epithelial progesterone receptor isoforms in embryo implantation. iScience 2021;24(12):103487. doi: 10.1016/j.isci.2021.103487.

Aruna M, Nagaraja T, Andal S, Tarakeswari S, Sirisha PV, Reddy AG, et al. Role of progesterone receptor polymorphisms in the recurrent spontaneous abortions: Indian case. PLoS One 2010;5(1):e8712. doi: 10.1371/journal.pone.0008712.

Su MT, Lin SH, Chen YC. Association of sex hormone receptor gene polymorphisms with recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril 2011;96(6):1435-44.e1. doi: 10.1016/j.fertnstert.2011.09.030.

Zeberg H, Kelso J, Paabo S. The Neandertal Progesterone Receptor. Mol Biol Evol 2020;37(9):2655-60. doi: 10.1093/molbev/msaa119.

Raghupathy R, Szekeres-Bartho J. Progesterone: A unique hormone with immunomodulatory roles in pregnancy. Int J Mol Sci 2022;23(3):1333. doi: 10.3390/ijms23031333.

Li J, Hong X, Mesiano S, Muglia LJ, Wang X, Snyder M, et al. Natural selection has differentiated the progesterone receptor among human populations. Am J Hum Genet 2018;103(1):45-57. doi: 10.1016/j.ajhg.2018.05.009.

Haas DM, Hathaway TJ, Ramsey PS. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev 2019(11):CD003511. doi: 10.1002/14651858.CD003511.pub5.

Devall AJ, Papadopoulou A, Podesek M, Haas DM, Price MJ, Coomarasamy A, et al. Progestogens for preventing miscarriage: a network meta-analysis. Cochrane Database Syst Rev 2021;4(4):CD013792. doi: 10.1002/14651858.CD013792.pub2.

Mahmutbegovic E, Marjanovic D, Medjedovic E, Mahmutbegović N, Dogan S, Valjevac A, et al. Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian women with pregnancy loss. BJBMS 2017;17(4):309-14. doi: 10.17305/bjbms.2017.1954.

Hanna CW, Bretherick KL, Liu CC, Stephenson MD, Robinson WP. Genetic variation within the hypothalamus-pituitary-ovarian axis in women with recurrent miscarriage. Hum Reprod 2010;25(10):2664-71. doi: 10.1093/humrep/deq211.

Su MT, Lee IW, Chen YC, Kuo PL. Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population. J Assist Reprod Genet 2011;28(3):239-43. doi: 10.1007/s10815-010-9510-8.

National Library of Medicine. Reference SNP (rs) Report. [cited 2024 December 7]. National Center for Biotechnology Information; [about rs1042838]. https://www.ncbi.nlm.nih.gov/snp/rs1042838#frequency_tab (14.01.2025).

Chen Z, Wang SH, Zhou J, Wu T, Li J. Contribution of PGR genetic polymorphisms to the pathogenesis of endometrial cancer: a meta-analysis. J Cancer Res Ther 2015;11(4):810-7. doi: 10.4103/0973-1482.146124.

Ghali RM, Al-Mutawa MA, Ebrahim BH, Jrah HH, Zaied S, Bhiri H, et al. Progesterone receptor (PGR) gene variants associated with breast cancer and associated features: a case-control study. Pathol Oncol Research 2020;26(1):141-7. doi: 10.1007/s12253-017-0379-z.

Golovchenko OV, Abramova MY, Orlova VS, Batlutskaya IV, Sorokina IN. Clinical and genetic characteristics of preeclampsia. Arch Razi Inst 2022;77(1):293-9. doi: 10.22092/ARI.2021.356481.1852.

Kadivnik M, Kralik K, Muller-Vranjes A, Vucemilovic-Juric V, Sijanovic S, Wagner J. Progesterone receptor genetic variants in pregnant women and fetuses as possible predictors of spontaneous premature birth: a preliminary case-control study. J Obstet Gynaecol Res 2022;48(5):1099-109. doi: 10.1111/jog.15194.

Schweikert A, Rau T, Berkholz A, Allera A, Daufeldt S, Wildt L. Association of progesterone receptor polymorphism with recurrent abortions. Eur J Obstet Gynecol Reprod Biol 2004;113(1):67-72. doi: 10.1016/j.ejogrb.2003.04.002.

Fishel S, Patel R, Lytollis A, Robinson J, Smedley M, Smith P, et al. Multicentre study of the clinical relevance of screening IVF patients for carrier status of the annexin A5 M2 haplotype. Reprod Biomed Online 2014;29(1):80-7. doi: 10.1016/j.rbmo.2014.03.019.

Sen S, Dixit A, Thakur C, Gokral J, Hinduja I, Zaveri K, et al. Association of progesterone receptor gene polymorphism with male infertility and clinical outcome of ICSI. J Assist Reprod Genet 2013;30(9):1133-9. doi: 10.1007/s10815-013-0074-2.

Dahdouh EM, Kutteh WH. Genetic testing of products of conception in recurrent pregnancy loss evaluation. Reprod Biomed Online 2021;43(1):120-6. doi: 10.1016/j.rbmo.2021.03.015.




DOI: https://doi.org/10.21164/pomjlifesci.1181

Copyright (c) 2025 Grażyna Adler, Mateusz Adler, Izabela Uzar, Emir Mahmutbegović

License URL: https://creativecommons.org/licenses/by-nc-nd/3.0/pl/