Association of rs1632944 and rs1632947 Polymor-phisms of the HLA-G Gene Promoter with Recurrent Spontaneous Abortion among Azerbaijani Women from Northwest Iran

Document Type : Original Article

Authors

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

10.22038/ijn.2024.72267.2401

Abstract

Background: Genetic polymorphisms are considered potential causes of recurrent spontaneous abortions (RSA). This study aimed to determine the frequencies and association of rs1632944 and rs1632947 polymorphisms of the HLA-G gene promoter region with the RSA in women from northwest Iran.
Methods: This case-control study was conducted on 180 women referred to Madar Infertility Center and Al-Zahra Hospital in Tabriz. Ninety patients with a history of at least two RSA as the patient group and 90 women with at least one child and no history of abortion as the control group were included in the study. 5 ml peripheral blood was obtained from each person; genomic DNA was extracted, amplified by PCR, and genotyped with sequencing and ARMS methods. Data were analyzed using SPSS, Chi-square, and Fisher's exact tests.
Results: For rs1632944 polymorphism, frequencies of the AA, AG, and GG genotypes were 34.44%, 45.55%, and 20% for the control group and 48.88%, 46.66%, and 4.44% for the patient group, respectively. We found that the minor allele G is recessive against major allele A and might protect women against RSA. For rs1632947 polymorphism, frequencies of the GG, AG, and AA genotypes were 52.22%, 35.55%, and 12.23% for the patient group and 64.44%, 32.22%, and 3.33% for the control group, respectively. We found that the minor allele A is recessive against the major allele G and is associated with the RSA.
Conclusion: The results showed that the rs1632944 and rs1632947 polymorphisms of the HLAG-G gene promoter, might be related to RSA in women from Northwest Iran.
 

Keywords

References

  1. Poras I, Yaghi L, Martelli-Palomino G, Mendes-Junior CT, Muniz YC, Cagnin NF, et al. Haplotypes of the HLA-G 3' untranslated region respond to endogenous factors of HLA-G+ and HLA-G- cell lines differentially. PloS one. 2017;12(1):e0169032.
  2. Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N. HLA-G: from biology to clinical benefits. Trends Immunol. 2008;29(3):125-132.
  3. González A, Rebmann V, LeMaoult J, Horn PA, Carosella ED, Alegre E. The immunosuppressive molecule HLA-G and its clinical implications. Crit Rev Clin Lab Sci. 2012;49(3):63-84.
  4. Kohn TP, Kohn JR, Darilek S, Ramasamy R, Lipshultz L. Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy. J Assist Reprod Genet. 2016;33(5):571-576.
  5. Hussain T, Murtaza G, Kalhoro DH, Kalhoro MS, Yin Y, Chughtai MI, et al. Understanding the Immune System in Fetal Protection and Maternal Infections during Pregnancy. J Immunol Res. 2022;2022: 7567708.
  6. Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990;248(4952):220-223.
  7. Mohammadi Bondarkhilli SA, Kordkatouli M, Maroufi M, Dulskas A. Oncogenic and anticancer roles of miRNAs in colorectal cancer: A review. Micro Nano Bio Aspects. 2024;3(1):14-22.
  8. Roumandeh N, Zare A, Saremi AT. Immunology of Recurrent Spontaneous Abortion. SJRM. 2018;3(2):121-12
  9. Ermert D, Blom AM. C4b-binding protein: The good, the bad and the deadly. Novel functions of an old friend. Immunol Lett. 2016;169:82-92.
  10. Shiina T, Hosomichi K, Inoko H, Kulski JK. The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet. 2009;54(1):15-39.
  11. Lee N, Malacko AR, Ishitani A, Chen MC, Bajorath J, Marquardt H, et al. The membrane-bound and soluble forms of HLA-G bind identical sets of endogenous peptides but differ with respect to TAP association. Immunity. 1995;3(5):591-600.
  12. Kofod L, Lindhard A, Bzorek M, Eriksen JO, Larsen LG, Hviid TVF. Endometrial immune markers are potential predictors of normal fertility and pregnancy after in vitro fertilization. Am J Reprod Immunol. 2017;78(3):
  13. Pfeiffer KA, Rebmann V, Pässler M, van der Ven K, van der Ven H, Krebs D, et al. Soluble HLA levels in early pregnancy after in vitro fertilization. Hum Immunol. 2000;61(6):559-564.
  14. Khalife D, Ghazeeri G, Kutteh W. Review of current guidelines for recurrent pregnancy loss: new strategies for optimal evaluation of women who may be superfertile. Semin Perinatol. 2019;43(2):105-115.
  15. Sato T, Sugiura-Ogasawara M, Ozawa F, Yamamoto T, Kato T, Kurahashi H, et al. Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Hum Reprod. 2020;35(1):255.
  16. Carosella ED, Rouas-Freiss N, Tronik-Le Roux D, Moreau P, LeMaoult J. HLA-G: An Immune Checkpoint Molecule. Adv Immunol. 2015;127:33-144.
  17. Carosella ED, Moreau P, Le Maoult J, Le Discorde M, Dausset J, Rouas-Freiss N. HLA-G molecules: from maternal-fetal tolerance to tissue acceptance. Adv Immunol. 2003;81:199-252.
  18. Castelli EC, Veiga-Castelli LC, Yaghi L, Moreau P, Donadi EA. Transcriptional and posttranscriptional regulations of the HLA-G gene. J Immunol Res. 2014;2014:734068.
  19. Castelli EC, de Almeida BS, Muniz YCN, Silva NSB, Passos MRS, Souza AS, et al. HLA-G genetic diversity and evolutive aspects in worldwide populations. Sci Rep. 2021;11(1):23070.
  20. Dias FC, Bertol BC, Poras I, Souto BM, Mendes-Junior CT, Castelli EC, et al. The genetic diversity within the 1.4 kb HLA-G 5' upstream regulatory region moderately impacts on cellular microenvironment responses. Sci Rep. 2018;8(1):5652.
  21. Berger DS, Hogge WA, Barmada MM, Ferrell RE. Comprehensive analysis of HLA-G: implications for recurrent spontaneous abortion. Reprod Sci. 2010;17(4):331-338.
  22. Phan L, Jin Y, Zhang H, Qiang W, Shekhtman E, Shao D. ALFA: Allele Frequency Aggregator. National Center for Biotechnology Information, U.S.: National Library of Medicine; 10 Mar. 2020. ncbi.nlm.nih.gov/snp/docs/gsr/alfa/.
  23. Merdas AH, Iqbal MN, Alyasiri NS. The Effects of HLA-G Gene Polymorphism and sHLA-G Level in Women with Threatened Abortion. J Tech. 2022;4(2):69-74.
  24. Ober C, Aldrich CL, Chervoneva I, Billstrand C, Rahimov F, Gray HL, et al. Variation in the HLA-G promoter region influences miscarriage rates. Am J Hum Genet. 2003;72(6):1425-1435.
  25. Nowak I, Wilczyńska K, Radwan P, Wiśniewski A, Krasiński R, Radwan M, et al. Association of soluble HLA-G Plasma level and HLA-G genetic polymorphism with pregnancy outcome of patients undergoing in vitrofertilization embryo transfer. Front Immunol. 2020;10:2982.
  26. Najafi Z, Feizi MA, Abbasaliizadeh S. Haplotype effect of two human leukocyte antigen-G polymorphisms of rs1736933 and rs2735022 on the recurrent pregnancy loss. J Inflamm Res. 2021; 24(5):398-409.
  27. Najafi Z, Kondori MK, Feizi MA, Abbasaliizadeh S. Association analysis of the HLA-G upstream polymorphism Rs1736933 with the recurrent spontaneous abortion. Journal of Babol University of Medical Sciences. 2020;22(1):175-1
  28. Khasevani L, Khalaj-Kondori M, Ebrahimi Behnam B. Association of rs2249863 and rs1233334 polymorphisms of the upstream region of HLA-G gene with recurrent spontaneous abortion in women from Northwest of Iran during 2018-2019. Iran J Obstet Gynecol Infertil. 2020;23(10):52-60.

  

Iranian Journal of Neonatology
Volume 16, Issue 2
April 2025
Pages 1-8

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