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CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss

Received: 8 August 2016     Accepted: 17 August 2016     Published: 5 September 2016
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Abstract

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is considered as a negative regulator of T cell activation and its role in maintaining immune tolerance is well established. The present case-control study aimed to investigate the CTLA-4 +49 A/G, -1661 A/G, -318 C/T and -1722 T/C single nucleotide polymorphisms (SNPs) and predisposition to recurrent pregnancy loss (RPL) in Gaza Strip - Palestine. The study was performed on 200 women with a history of two or more pregnancy losses (case group) and 200 control women with at least two live births and without any previous history of abortion. PCR-based restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping CTLA-4 polymorphisms. Study results revealed that there is no significant association between the allele/genotype frequencies of the four investigated CTLA-4 SNPs and RPL. This trend remained true under dominant, co-dominant and recessive models. The A\G genotype of -1661 A\G polymorphism was higher in patients (45%) as compared to controls (39.5%) but without statistical significance. The minor allele frequencies (MAFs) of the CTLA-4 gene polymorphisms in the patient/control group were as follows: +49A>G: 0.22/0.22, -318 C>T: 0.15/0.11, -1661 A>G: 0.30/0.26 and -1722 T>C: 0.08/0.08. The four investigated CTLA-4 polymorphisms do not contribute to the risk of RPL in the study population. Testing other CTLA-4 gene polymorphisms and the level of CTLA-4 expression in RPL patients is recommended.

Published in International Journal of Genetics and Genomics (Volume 4, Issue 4)
DOI 10.11648/j.ijgg.20160404.11
Page(s) 31-35
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2016. Published by Science Publishing Group

Keywords

Recurrent Pregnancy Loss, CTLA-4, Gene Polymorphism, PCR-RFLP

References
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[2] Li, T. C., Makris, M., Tomsu, M., Tuckerman, E., & Laird, S. (2002). Recurrent miscarriage: aetiology, management and prognosis. Human reproduction update, 8(5), 463-481.
[3] ‏Riella, L. V., Dada, S., Chabtini, L., Smith, B., Huang, L., Dakle, P., Mfarrej, B., D'Addio, F., Adams, L. T., Kochupurakkal, N., Vergani, A., Fiorina, P., Mellor, A. L., Sharpe, A. H., Yagita, H.,& Guleria, A. (2013). B7h (ICOS-L) maintains tolerance at the fetomaternal interface. The American journal of pathology, 182(6), 2204-2213.
[4] Jain, N., Nguyen, H., Chambers, C., & Kang, J. (2010). Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity. Proceedings of the National Academy of Sciences, 107(4), 1524-1528.‏
[5] Gupta, R., Prakash, S., Parveen, F., & Agrawal, S. (2012). Association of CTLA-4 and TNF-α polymorphism with recurrent miscarriage among North Indian women. Cytokine, 60(2), 456-462.
[6] Bonyadi, M., Parsa, S., Taghavi, S., & Zeinalzadeh, N. (2014). Studies on the relationship of CTLA-4+ 49A/G gene with Recurrent Miscarriage in Northwest of Iran. Molecular and Biochemical Diagnosis (Journal), 1(3), 171-176.
[7] Dias, F. C., Medina, T. D. S., Mendes-Junior, C. T., Dantas, R. O., Pissetti, C. W., Junior, V. R., Joviliano, R. D., Marin-Neto, J. A., Gutierrez, R. S., Moreau, P., Donadi, E. A., & Silva, J. S. (2013). Polymorphic sites at the immunoregulatory CTLA-4 gene are associated with chronic chagas disease and its clinical manifestations. PloS one, 8(10), e78367.
[8] ‏Dehaghani, A. S., Doroudchi, M., Kalantari, T., Pezeshki, A. M., & Ghaderi, A. (2005). Heterozygosity in CTLA-4 gene and severe preeclampsia. International Journal of Gynecology and Obstetrics, 88(1), 19-24.
[9] Wang, X., Lin, Q., Ma, Z., Hong, Y., Zhao, A., Di, W., & Lu, P. (2005). Association of the A/G Polymorphism at Position 49 in Exon 1 of CTLA-4 with the Susceptibility to Unexplained Recurrent Spontaneous Abortion in the Chinese Population. American Journal of Reproductive Immunology, 53(2), 100-105.
[10] Naderi, F., Kazemi, T., Fatemi, R., Zarei, S., & Idali, F. (2014). P-212: Association between Polymorphisms of CTLA-4 Gene and Unexplained Recurrent Spontaneous Abortion in An Iranian Population. Cell j (Yakhteh), 7(3), 223-223.
[11] Jääskeläinen, E., Toivonen, S., Keski-Nisula, L., Paattiniemi, E. L., Helisalmi, S., Punnonen, K., & Heinonen, S. (2008). CTLA-4 polymorphism 49A–G is associated with placental abruption and preeclampsia in Finnish women. Clinical Chemical Laboratory Medicine, 46(2), 169-173.
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  • APA Style

    Eman N. Helles, Mohammed J. Ashour, Fadel A. Sharif. (2016). CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss. International Journal of Genetics and Genomics, 4(4), 31-35. https://doi.org/10.11648/j.ijgg.20160404.11

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    ACS Style

    Eman N. Helles; Mohammed J. Ashour; Fadel A. Sharif. CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss. Int. J. Genet. Genomics 2016, 4(4), 31-35. doi: 10.11648/j.ijgg.20160404.11

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    AMA Style

    Eman N. Helles, Mohammed J. Ashour, Fadel A. Sharif. CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss. Int J Genet Genomics. 2016;4(4):31-35. doi: 10.11648/j.ijgg.20160404.11

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  • @article{10.11648/j.ijgg.20160404.11,
      author = {Eman N. Helles and Mohammed J. Ashour and Fadel A. Sharif},
      title = {CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss},
      journal = {International Journal of Genetics and Genomics},
      volume = {4},
      number = {4},
      pages = {31-35},
      doi = {10.11648/j.ijgg.20160404.11},
      url = {https://doi.org/10.11648/j.ijgg.20160404.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20160404.11},
      abstract = {Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is considered as a negative regulator of T cell activation and its role in maintaining immune tolerance is well established. The present case-control study aimed to investigate the CTLA-4 +49 A/G, -1661 A/G, -318 C/T and -1722 T/C single nucleotide polymorphisms (SNPs) and predisposition to recurrent pregnancy loss (RPL) in Gaza Strip - Palestine. The study was performed on 200 women with a history of two or more pregnancy losses (case group) and 200 control women with at least two live births and without any previous history of abortion. PCR-based restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping CTLA-4 polymorphisms. Study results revealed that there is no significant association between the allele/genotype frequencies of the four investigated CTLA-4 SNPs and RPL. This trend remained true under dominant, co-dominant and recessive models. The A\G genotype of -1661 A\G polymorphism was higher in patients (45%) as compared to controls (39.5%) but without statistical significance. The minor allele frequencies (MAFs) of the CTLA-4 gene polymorphisms in the patient/control group were as follows: +49A>G: 0.22/0.22, -318 C>T: 0.15/0.11, -1661 A>G: 0.30/0.26 and -1722 T>C: 0.08/0.08. The four investigated CTLA-4 polymorphisms do not contribute to the risk of RPL in the study population. Testing other CTLA-4 gene polymorphisms and the level of CTLA-4 expression in RPL patients is recommended.},
     year = {2016}
    }
    

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  • TY  - JOUR
    T1  - CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss
    AU  - Eman N. Helles
    AU  - Mohammed J. Ashour
    AU  - Fadel A. Sharif
    Y1  - 2016/09/05
    PY  - 2016
    N1  - https://doi.org/10.11648/j.ijgg.20160404.11
    DO  - 10.11648/j.ijgg.20160404.11
    T2  - International Journal of Genetics and Genomics
    JF  - International Journal of Genetics and Genomics
    JO  - International Journal of Genetics and Genomics
    SP  - 31
    EP  - 35
    PB  - Science Publishing Group
    SN  - 2376-7359
    UR  - https://doi.org/10.11648/j.ijgg.20160404.11
    AB  - Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is considered as a negative regulator of T cell activation and its role in maintaining immune tolerance is well established. The present case-control study aimed to investigate the CTLA-4 +49 A/G, -1661 A/G, -318 C/T and -1722 T/C single nucleotide polymorphisms (SNPs) and predisposition to recurrent pregnancy loss (RPL) in Gaza Strip - Palestine. The study was performed on 200 women with a history of two or more pregnancy losses (case group) and 200 control women with at least two live births and without any previous history of abortion. PCR-based restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping CTLA-4 polymorphisms. Study results revealed that there is no significant association between the allele/genotype frequencies of the four investigated CTLA-4 SNPs and RPL. This trend remained true under dominant, co-dominant and recessive models. The A\G genotype of -1661 A\G polymorphism was higher in patients (45%) as compared to controls (39.5%) but without statistical significance. The minor allele frequencies (MAFs) of the CTLA-4 gene polymorphisms in the patient/control group were as follows: +49A>G: 0.22/0.22, -318 C>T: 0.15/0.11, -1661 A>G: 0.30/0.26 and -1722 T>C: 0.08/0.08. The four investigated CTLA-4 polymorphisms do not contribute to the risk of RPL in the study population. Testing other CTLA-4 gene polymorphisms and the level of CTLA-4 expression in RPL patients is recommended.
    VL  - 4
    IS  - 4
    ER  - 

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Author Information
  • Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine

  • Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine

  • Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine

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