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FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

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Abstract

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case–control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

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References

  1. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76–83.

    PubMed  PubMed Central  Google Scholar 

  2. Kiwi R. Recurrent pregnancy loss: evaluation and discussion of the causes and their management. Cleve Clin J Med. 2006; 73(10):913–921.

    Article  PubMed  Google Scholar 

  3. Aschkenazi S, Straszewski S, Verwer KM, et al. Differential regulation and function of the Fas/Fas ligand system in human trophoblast cells. Biol Reprod. 2002;66(6):1853–1861.

    Article  CAS  PubMed  Google Scholar 

  4. Abrahams VM, Straszewski-Chavez SL, Guller S, Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod. 2004;10(1):55–63.

    Article  CAS  PubMed  Google Scholar 

  5. Crocker IP, Cooper S, Ong SC, Baker PN. Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol. 2003;162(2):637–643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hoshimoto K, Hayashi M, Ohkura T. Plasma levels of soluble Fas during normal pregnancy. Gynecol Obstet Invest. 2001;51(2): 96–98.

    Article  CAS  PubMed  Google Scholar 

  7. Zong WX, Thompson CB. Necrotic death as a cell fate. Genes Dev. 2006;20(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  8. Choi HK, Choi BC, Lee SH, Kim JW, Cha KY, Baek KH. Expression of angiogenesis- and apoptosis-related genes in chorionic villi derived from recurrent pregnancy loss patients. Mol Reprod Dev. 2003;66(1):24–31.

    Article  CAS  PubMed  Google Scholar 

  9. Levy R, Nelson DM. To be, or not to be, that is the question. Apoptosis in human trophoblast. Placenta. 2000;21(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  10. Patel T, Gores GJ. Apoptosis in liver transplantation: a mechanism contributing to immune modulation, preservation injury, neoplasia, and viral disease. Liver Transpl Surg. 1998;4(1):42–50.

    Article  CAS  PubMed  Google Scholar 

  11. Neale DM, Mor G. The role of Fas mediated apoptosis in preeclampsia. J Perinat Med. 2005;33(6):471–477.

    Article  CAS  PubMed  Google Scholar 

  12. Minas V, Jeschke U, Kalantaridou SN, et al. Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin. Mol Hum Reprod. 2007;13(9):663–673.

    Article  CAS  PubMed  Google Scholar 

  13. Sun T, Zhou Y, Li H, et al. FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer. J Exp Med. 2005;202(7):967–974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wu J, Metz C, Xu X, et al. A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J Immunol. 2003; 170(1):132–138.

    Article  CAS  PubMed  Google Scholar 

  15. Liakouli V, Manetti M, Pacini A, et al. The -670G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis. Ann Rheum Dis. 2009;68(4): 584–590.

    Article  CAS  PubMed  Google Scholar 

  16. Kang S, Dong SM, Seo SS, Kim JW, Park SY. FAS -1377 G/A polymorphism and the risk of lymph node metastasis in cervical cancer. Cancer Genet Cytogenet. 2008;180(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  17. Li C, Larson D, Zhang Z, et al. Polymorphisms of the FAS and FAS ligand genes associated with risk of cutaneous malignant melanoma. Pharmacogenet Genomics. 2006;16(4):253–263.

    Article  PubMed  Google Scholar 

  18. Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991;11(3):298–300, 302.

    CAS  PubMed  Google Scholar 

  19. Fuks A, Parton LA, Polavarapu S, et al. Polymorphism of Fas and Fas ligand in preterm premature rupture of membranes in singleton pregnancies. Am J Obstet Gynecol. 2005;193(3 pt 2): 1132–1136.

    Article  CAS  PubMed  Google Scholar 

  20. Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990;11(2):116–128.

    Article  CAS  PubMed  Google Scholar 

  21. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol 2000;96(2): 271–276.

    CAS  PubMed  Google Scholar 

  23. Hammer A, Blaschitz A, Daxbock C, Walcher W, Dohr G. Fas and Fas-ligand are expressed in the uteroplacental unit of first-trimester pregnancy. Am J Reprod Immunol. 1999; 41(1):41–51.

    Article  CAS  PubMed  Google Scholar 

  24. Eide IP, Isaksen CV, Salvesen KA, et al. Fetal growth restriction is associated with reduced FasL expression by decidual cells. J Reprod Immunol 2007;74(1–2):7–14.

    Article  CAS  PubMed  Google Scholar 

  25. Turner AK, Begon M, Jackson JA, Bradley JE, Paterson S. Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population. PLoS Genet. 2011;7(10):e1002343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Novakovic B, Saffery R. The ever growing complexity of placental epigenetics - Role in adverse pregnancy outcomes and fetal programming. Placenta. 2012;33(12):959–970.

    Article  CAS  PubMed  Google Scholar 

  27. Hebert DN, Molinari M. In and out of the ER: protein folding, quality control, degradation, and related human diseases. Physiol Rev. 2007;87(4):1377–1408.

    Article  CAS  PubMed  Google Scholar 

  28. Ciarmela P, Boschi S, Bloise E, et al. Polymorphisms of FAS and FAS ligand genes in preeclamptic women. Eur J Obstet Gynecol Reprod Biol. 2010;148(2):144–146.

    Article  CAS  PubMed  Google Scholar 

  29. Nair RR, Khanna A, Singh K. Association of FAS -1377 G>A and FAS -670 A>G functional polymorphisms of FAS gene of cell death pathway with recurrent early pregnancy loss risk. J Reprod Immunol. 2012;93(2):114–118.

    Article  CAS  PubMed  Google Scholar 

  30. Huang QR, Morris D, Manolios N. Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene. Mol Immunol. 1997;34(8–9): 577–582.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Rosiane Mattar MD, PhD.

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Banzato, P.C.A., Daher, S., Traina, É. et al. FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss. Reprod. Sci. 20, 1111–1115 (2013). https://doi.org/10.1177/1933719113477488

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