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Cytotoxic T-lymphocyte Associated Antigen-4 (CTLA-4) Polymorphism, Cancer, and Autoimmune Diseases

1 Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, U.S.A.

Immune system dysfunction is one of the key features in onset and development of cancer and autoimmunity. Cytotoxic T-lymphocyte-antigen-4 (CTLA-4), as a leader immune checkpoint plays a crucial effects in the regulation of immune suppression and tolerance. In this review, role of CTLA-4 and its three important polymorphisms (SNP), CTLA-4 +49A/G, CTLA-4 CT60 A/G and CTLA-4 −318C/T in development of cancer and autoimmune diseases have been discussed. The evidences revealed that CTLA-4 +49A/G, A allele increases the risk of cervical cancer and CTLA-4 +49A/G G allele decreases the risk of breast cancer in Asian population. The presence of G allele of CTLA-4 +49A/G SNP is strongly correlates with increased risk of Graves and systemic lupus erythematous (SLE), in Asian and European population. G allele of CTLA-4 +49A/G SNP may be a risk factor for rheumatoid arthritis susceptibility (RA). Evidence suggests that the presence of CTLA-4 +49 G allele reduces the inhibitory function of CTLA-4 on T cells. Therefore, it is logical to propose that G allele of CTLA-4 +49 A/G increases the immune system activity and decreases the risk of cancer. The evidence on the effect of CTLA-4 CT60 A/G SNP on the risk of cancer development and autoimmune disorders is inconclusive. No association was found between the CTLA-4 −318C/T polymorphism with autoimmune diseases.
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Keywords CTLA-4; cancer; autoimmunity; polymorphism; Graves

Citation: Maryam Tanhapour, Asad Vaisi-Raygani, Mozafar Khazaei, Zohreh Rahimi, Tayebeh Pourmotabbed. Cytotoxic T-lymphocyte Associated Antigen-4 (CTLA-4) Polymorphism, Cancer, and Autoimmune Diseases. AIMS Medical Science, 2017, 4(4): 395-412. doi: 10.3934/medsci.2017.4.395


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