Haplotype Effect of Two Human Leukocyte Antigen-G Polymorphisms of rs1736933 and rs2735022 on the Recurrent Pregnancy Loss

authors:

avatar Zahra Najafi 1 , avatar mohammad khalaj-kondori ORCID 1 , * , avatar Mohammad Ali Hosseinpour Feizi 1 , avatar Shamsi Abbasaliizadeh 2

Department of Animal Sciences, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Gynecology ;Obstetrics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Journal of Inflammatory Diseases: Vol.24, issue 5; 398-409
article type: issue_documents_importer

how to cite: Najafi Z, khalaj-kondori M, Hosseinpour Feizi M A, Abbasaliizadeh S. Haplotype Effect of Two Human Leukocyte Antigen-G Polymorphisms of rs1736933 and rs2735022 on the Recurrent Pregnancy Loss. J Inflamm Dis. 2020;24(5):e156240. 

Abstract

Background: Recurrent Pregnancy Loss (RPL) is a multifactorial disease that affects 1-3% of couples. Since Human Leukocyte Antigen-G (HLA-G) gene is involved in fetal maternal immune tolerance, mutations in the HLA-G gene can affect the success rate of pregnancy. Objective: The present study aims to investigate the haplotype effect of rs1736933 and rs2735022 polymorphisms found in the HLA-G gene on the RPL. Methods In this case-control study, participants were 100 women with RPL and 80 women with normal fertility in northwestern Iran. The HLA-G gene promoter was amplified by Polymerase Chain Reaction (PCR) method and sequenced. The genotype and allele frequencies of the two polymorphisms were compared between the two groups by using t-test in SPSS software version 22. Haplotype analysis was performed using PHASE 2.1 and Haploview 4.2 applications Findings: C allele and CC genotype in rs2735022 polymorphism and the G allele and GG genotype in rs1736933 polymorphism showed a significant association with the RPL (P<0.05). Frequency of haplotypes AA, AC, GA, GC were 0.72, 0.23, 0.01, 0.03 in patients and 0.39, 0.01, 0.02, 0.59 in the control group (P<0.05). The linkage disequilibrium score was 94. Conclusion: Analysis of GC haplotype in rs2735022 and rs1736933 polymorphisms of the HLA-G gene can be helpful in genetic studies of women with RPL.

References

  • 1.

    Ghanami Gashti N, Salehi Z, Zahiri Sorouri Z, Eskafi Sabet E. Analysis of 4977-bp mitochondrial DNA deletion in the women with spontaneous abortion. J Guilan Univ Med Sci. 2014; 22(88):1-6. [In Persian] http://journal.gums.ac.ir/article1-412-en.html.

  • 2.

    Keirse MJ, Rush RW, Anderson AB, Turnbull AC. Risk of preterm delivery in patients with previous pre-term delivery and/or abortion. Br J Obstet Gynaecol. 1978; 85(2):81-5. [DOI:10.1111/j.1471-0528.1978.tb10457.x] [PMID].

  • 3.

    Alemayehu M, Yebyo H, Medhanyie AA, Bayray A, Fantahun M, Goba GK. Determinants of repeated abortion among women of reproductive age attending health facilities in Northern Ethiopia: A case-control study. BMC Public Health. 2017; 17(1):188. [DOI:10.1186/s12889-017-4106-1] [PMID] [PMCID].

  • 4.

    Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N. HLAG: From biology to clinical benefits. Trends Immunol. 2008; 29(3):125-32. [DOI:10.1016/j.it.2007.11.005] [PMID].

  • 5.

    Pokale YS. Recurrent miscarriage. Int Res J Med Sci. 2015; 3(9):13-9. http://www.isca.in/MEDI_SCI/Archive/v3/i9/2. ISCA-IRJMedS-2015-036.php.

  • 6.

    Vaiman D. Genetic regulation of recurrent spontaneous abortion in humans. Biomed J. 2015; 38(1):11-24. [DOI:10.4103/2319-4170.133777] [PMID].

  • 7.

    Le Bouteiller P, Sargent IL. HLA class I molecules in the placenta: which ones, where and what for? A workshop report. Placenta. 2000; 21 Suppl A:S93-6. [DOI:10.1053/plac.1999.0530] [PMID].

  • 8.

    Carosella ED, LeMaoult J. HLA-G: A look back, a look forward. Cell Mol Life Sci. 2011; 68(3):337-40. [DOI:10.1007/s00018010-0577-2] [PMID].

  • 9.

    Shah I, hman E. Unsafe abortion: Global and regional incidence, trends, consequences, and challenges. J Obstet Gynaecol Can. 2009; 31(12):1149-58. [DOI:10.1016/S17012163(16)34376-6].

  • 10.

    Daher S, Mattar R, Gueuvoghlanian-Silva BY, Torloni MR. Genetic polymorphisms and recurrent spontaneous abortions: An overview of current knowledge. Am J Reprod Immunol. 2012; 67(4):341-7. [DOI:10.1111/j.1600-0897.2012.01123.x] [PMID].

  • 11.

    Ellis SA, Sargent IL, Redman CW, McMichael AJ. Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology. 1986; 59(4):595601. [PMID] [PMCID].

  • 12.

    Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the interface of maternal-fetal tolerance. Trends Immunol. 2017; 38(4):272-86. [DOI:10.1016/j.it.2017.01.009] [PMID].

  • 13.

    Craenmehr MHC, Nederlof I, Cao M, Drabbels JJM, SpruytGerritse MJ, Anholts JDH, et al. Increased HLA-G expression in term placenta of women with a history of recurrent miscarriage despite their genetic predisposition to decreased HLA-G levels. Int J Mol Sci. 2019; 20(3):625. [DOI:10.3390/ ijms20030625] [PMID] [PMCID].

  • 14.

    Mosaferi E, Majidi J, Mohammadian M, Babaloo Z, Monfaredan A, Baradaran B. HLA-G expression pattern: Reliable assessment for pregnancy outcome prediction. Adv Pharm Bull. 2013; 3(2):443-6. [DOI:10.5681/apb.2013.072] [PMID] [PMCID.

  • 15.

    LeMaoult J, Le Discorde M, Rouas-Freiss N, Moreau P, Menier C, McCluskey J, et al. Biology and functions of human leukocyteantigen-G in health and sickness. Tissue Antigens. 2003; 62(4):273-84. [DOI:10.1034/j.1399-0039.2003.00143.x] [PMID.

  • 16.

    Donadi EA, Castelli EC, Arnaiz-Villena A, Roger M, Rey D, Moreau P. Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association. Cell Mol Life Sci. 2011; 68(3):369-95. [DOI:10.1007/s00018-010-0580-7] [PMID] [PMCID].

  • 17.

    Berger DS. Molecular associations of recurrent spontaneous abortion [PhD. dissertation]. Pittsburgh, PA: University of Pittsburgh; 2007. http://d-scholarship.pitt.edu/10015/.

  • 18.

    Lau HH, Ng NHJ, Loo LSW, Jasmen JB, Teo AKK. The molecular functions of hepatocyte nuclear factors - In and beyond the liver. J Hepatol. 2018; 68(5):1033-48. [DOI:10.1016/j. jhep.2017.11.026] [PMID].

  • 19.

    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):1425-35. [DOI:10.1086/375501] [PMID] [PMCID].

  • 20.

    Yazdani N, Shekari Khaniani M, Bastami M, Ghasemnejad T, Afkhami F, Mansoori Derakhshan S. HLA-G regulatory variants and haplotypes with susceptibility to recurrent pregnancy loss. Int J Immunogenet. 2018; 45(4):181-9. [DOI:10.1111/iji.12364] [PMID].

  • 21.

    Hviid TV, Rizzo R, Christiansen OB, Melchiorri L, Lindhard A, Baricordi OR. HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics. 2004; 56(3):13541. [DOI:10.1007/s00251-004-0673-2] [PMID].

  • 22.

    Dias FC, Bertol BC, Poras I, Souto BM, Mendes-Junior CT, Castelli EC, et al. The genetic diversity within the 1.4 kb HLAG 5 upstream regulatory region moderately impacts on cellular microenvironment responses. Sci Rep. 2018; 8(1):5652. [DOI:10.1038/s41598-018-24009-7] [PMID] [PMCID].

  • 23.

    Sipak O, Ry A, Grzywacz A, Laszczyska M, Zimny M, Karakiewicz B, et al. The relationship between the HLA-G polymorphism and sHLA-G levels in parental pairs with high-risk pregnancy. Int J Environ Res Public Health. 2019; 16(9):1546. [DOI:10.3390/ ijerph16091546] [PMID] [PMCID].

  • 24.

    Castelli EC, Ramalho J, Porto IO, Lima TH, Felcio LP, Sabbagh A, et al. Insights into HLA-G genetics provided by worldwide haplotype diversity. Front Immunol. 2014; 5:476. [DOI:10.3389/ fimmu.2014.00476] [PMID] [PMCID].

  • 25.

    Noci I, Fuzzi B, Rizzo R, Melchiorri L, Criscuoli L, Dabizzi S, et al. Embryonic soluble HLA-G as a marker of developmental potential in embryos. Human Reprod. 2005; 20(1):138-46. [DOI:10.1093/humrep/deh572] [PMID].

  • 26.

    Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3):1215. [DOI:10.1093/nar/16.3.1215] [PMID] [PMCID].

  • 27.

    Tan Z, Shon AM, Ober C. Evidence of balancing selection at the HLA-G promoter region. Hum Mol Genet. 2005; 14(23):3619-28. [DOI:10.1093/hmg/ddi389] [PMID].

  • 28.

    Berger DS, Hogge WA, Barmada MM, Ferrell RE. Comprehensive analysis of HLA-G: Implications for recurrent spontaneous abortion. Reprod Sci. 2010; 17(4):331-8. [DOI:10.1177/1933719109356802] [PMID].

  • 29.

    Agrawal D, Prakash S, Misra MK, Phadke SR, Agrawal S. Implication of HLA-G 5 upstream regulatory region polymorphisms in idiopathic recurrent spontaneous abortions. Reprod Biomed Online. 2015; 30(1):82-91. [DOI:10.1016/j.rbmo.2014.09.015] [PMID].

  • 30.

    Quintero-Ronderos P, Laissue P. Genetic variants contributing to early recurrent pregnancy loss etiology identified by sequencing approaches. Reprod Sci. 2019; 1933719119831769. [DOI:10.1177/1933719119831769] [PMID].

  • 31.

    Wang X, Biernacka JM. Assessing the effects of multiple markers in genetic association studies. Front Genet. 2015; 6:66. [DOI:10.3389/fgene.2015.00066] [PMID] [PMCID].

  • 32.

    Karimzadeh Meybodi MA, Taheripanah R. Infections in Recurrent Miscarriage. J Reprod Infertil. 2000; 1(2):24-34. [In Persian] https://www.jri.ir/article/327##.