CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss
International Journal of Genetics and Genomics
Volume 4, Issue 4, August 2016, Pages: 31-35
Received: Aug. 8, 2016; Accepted: Aug. 17, 2016; Published: Sep. 5, 2016
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Authors
Eman N. Helles, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine
Mohammed J. Ashour, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine
Fadel A. Sharif, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Islamic University of Gaza, Gaza, Palestine
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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.
Keywords
Recurrent Pregnancy Loss, CTLA-4, Gene Polymorphism, PCR-RFLP
To cite this article
Eman N. Helles, Mohammed J. Ashour, Fadel A. Sharif, CTLA-4 Gene Polymorphism in Women with Idiopathic Recurrent Pregnancy Loss, International Journal of Genetics and Genomics. Vol. 4, No. 4, 2016, pp. 31-35. doi: 10.11648/j.ijgg.20160404.11
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Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
References
[1]
Rasti, Z., & Nasiri, M. (2016). Association of the +49 A/G Polymorphism of CTLA-4 Gene with Idiopathic Recurrent Spontaneous Abortion in Women in Southwest of Iran. J Reprod Infertil. 17(3): 151–156.
[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.
[12]
Tsai, A. F., Kaufman, K. A., Walker, M. A., Karrison, T. G., Odem, R. R., Barnes, R. B., Scott, J. R., Schreiber, J. R., Stephenson, M. D., & Ober, C. (1998). Transmission disequilibrium of maternally-inherited CTLA-4 microsatellite alleles in idiopathic recurrent miscarriage. Journal of reproductive immunology, 40(2), 147-157.
[13]
Ghaderi, A. (2011). CTLA4 gene variants in autoimmunity and cancer: a comparative review. Iranian Journal of Immunology, 8(3), 127-127.
[14]
Sun, T., Hu, Z., Shen, H., & Lin, D. (2009). Genetic polymorphisms in cytotoxic T-lymphocyte antigen 4 and cancer: the dialectical nature of subtle human immune dysregulation. Cancer research, 69(15), 6011-6014.
[15]
Wang, X. B., Pirskanen, R., Giscombe, R., & Lefvert, A.K. (2008). Two SNPs in the promoter region of the CTLA-4 gene affect binding of transcription factors and are associated with human myasthenia gravis. Journal of internal medicine, 263(1), 61-69.
[16]
Pastuszak-Lewandoska, D., Domanska, D., Rudzinska, M., Bossowski, A., Kucharska, A., Sewerynek, E., Czarnecka, K., Migdalska-Sęk, M., & Czarnocka, B. (2013). CTLA-4 polymorphisms (+ 49 A/G and-318 C/T) are important genetic determinants of AITD susceptibility and predisposition to high levels of thyroid autoantibodies in Polish children-preliminary study. Acta Biochim Pol, 60(4), 641-646.
[17]
Chaili (2010). Association of CTLA-4 gene polymorphisms with recurrent spontaneous abortion, (Unpublished Master Thesis). Ningxia medical university-China, Accessed March 10, 2016 from dissertation topic website, http://www.dissertationtopic.net/doc/83153
[18]
Pendeloski, K. P., Sass, N., Torloni, M. R., Mattar, R., Moron, A. F., Franchim, C. S., & Daher, S. (2011). Immunoregulatory gene polymorphisms in women with preeclampsia. Hypertension Research, 34(3), 384-388.
[19]
Hayashi, Y., Matsukawa, Y., Kitaori, T., Katano, K., Ozaki, Y., & Sugiura, M. (2015). Genotyping analyses for polymorphisms of PD-1 gene and CTLA4 gene in patients with recurrent pregnancy loss. Human Reproduction, 30, 191-191.
[20]
Messaoudi, S., Houas, I., Yaseen, K., Dandana, M., & Mahjoub, T. (2014). CTLA-4 gene polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population. BMC Genomics, 15(Suppl 2), P11. doi: 10.1186/1471-2164-15- S2-P11.
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