ASSOCIATION BETWEEN POLYMORPHISM IN CYTOTOXIC T LYMPHOCYTE ANTIGEN -4 GENE AND THE RISK OF RHEUMATOID ARITHRITIS IN IRAQI PATIENTS
DOI:
https://doi.org/10.36103/ijas.v53i2.1531Keywords:
RA, CTLA-4, CT60, 49, genotypeAbstract
CTLA4 is well known that it is expressed in activated T-lymphocyte, and can be distinguished in cancer phenomena as well as many chronic diseases. This study was designed aiming to find a correlation between CTLA-4 and Rheumatoid Arthritis (RA). This research was carried out at Baghdad Teaching Hospital, Medical City, Baghdad, Iraq. In this study, 245 patients diagnosed with rheumatoid arthritis and 188 healthy volunteers' individuals (control group) were selected randomly. The diagnosis of the RA to both patients group and healthy individuals were characterized according to a certain protocols. The sequence of four (JO31, CT60, +49, and MH30 genotypes) were carried out using PCR-DGGE. The polymorphisms (SNPs) were genotyped for the control and the patients and the distribution of the genotypes was carried out according to HWE (P<0.05) for the two groups. The effect of two alleles on the susceptibility of RA, were investigated thoroughly, and there was a major association between the CT60, +49 alleles with the risk of RA (OR 1.43, 95%Cl (1.14-1.89), and the P-value 0.004 for CT60), while for +49 it was (OR 1.38, 95%Cl (1.04-1.77) and the P-value 0.009). There is a significant correlation between CTLA-4 genes and Rheumatoid Arthritis (RA) and both CT60 and +49 can be the main reason for RA, while JO31 and MH30 are not associated with CTLA-4.
References
Abdel Galil SM and HA Hagrass.2014. The Role of CTLA-4 Exon-1 49 A/G Polymorphism and Soluble CTLA-4 Protein Level in Egyptian Patients with Behçet's Disease. Biomed Research International. 2014: 513915. doi: 10.1155/2014/513915
AL-Hamdani H. and A AL-Hashimy.2020. Molecular detection of UREC, HPMA, RSBA AND MRPA genes of Proteus Mirabilis urinary tract infection in patient with rheumatoid arthritis. Iraqi Journal Of Agricultural Scineces. 51(Special Issue). 245-251
Arnett FC,SM Edworthy and DA Bloch.1988. The American rheumatism association 1987 revised criteria for the classification of the rheumatoid arthritis. Arthritis Rheum (31): 315- 324
Buchbinder EI and A Desai.2016. CTLA-4 and PD-1 Pathways. American Journal of Clinical Oncology. 39(1): 98-106.
Cozara JM, JM Romerob, N Aptsiaurib, F Vazqueza and et al.2007. High incidence of CTLA-4 AA (CT60) polymorphism in renal cell cancer. Human Immunology. 68: 698-704.
Ghapanchi J, MR Haghshenas, H Ghaderi, S Amanpour and et al.2014. CTLA-4 Gene Polymorphism in +49 A/G Position: A Case Control Study on Patients with Oral Lichen Planus. Journal of International Oral Health. 6(5): 17-21
Gottenberg J-E, P Loiseau, M Azarian, C Chen and et al.2007. CTLA-4 +49A/G and CT60 gene polymorphisms in primary Sjögren syndrome. Arthritis Research and Therapy. 9(2): R24.
Gough SC, LS Walker and DM Sansom.2005. CTLA4 gene polymorphism and autoimmunity. Immunology Reviews. (204): 102-115
GTEx Consortium. Human genomics.2015. The Genotype-Tissue Expression (GTEx) pilot analysis: multi tissue gene regulation in humans. Science. (348): 648–660
Hannani D, M Vétizou, D Enot, S Rusakiewicz and et al.2015. Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25. Cell Research. 25(2): 208–224
Hunt KA, DP McGovern, PJ Kumar, S Ghosh and et al.2005. A common CTLA4 haplotype associated with coeliac disease. European Journal of Human Genetics. 13(4): 440-4.
Ishigaki K, Y Kochi, A Suzuki and et al.2017. Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis. Nature Genetics. (49): 1120-1125
Jasim R.A., M. A. Umran and E. H. Humadi. 2020. Detection of vaspin RS2236242 and chemerin RS17173608 gene polymorphism in a sample of obese Iraqi polycystic ovarian syndrome women. Iraqi Journal of Agricultural Sciences .51(1):462-469
Jia X-H, L-Y Geng, P-P Jiang, H Xu and et al. 2020. The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors. Journal of Experimental & Clinical Cancer Research. (39): 284.
Jing Su, Li Yan , Su Guanglong ,J Wang, T Qiu.2018.Genetic association of CTLA4 gene with polycystic ovary syndrome in the Chinese Han population. Medicine. 97: 29(e11422).
Kailashiya V, HB Sharma , J Kailashiya.2019. Role of CTLA4 A49G polymorphism in systemic lupus erythematosus and its geographical distribution. Journal of Clinical Pathology. 10: 659-662.
Kailashiya V, HB Sharma , J Kailashiya . 2019.Role of CTLA4 A49G polymorphism in systemic lupus erythematosus and its geographical distribution. Journal of Clinical Pathology. 72: 659-662
Karami J, S Aslani, A Jamshidi, M Garshasbi and M Mahmoudi.2019. Genetic implications in the pathogenesis of rheumatoid arthritis; an updated review. Gene. (20)702:8-16.
Kouki T, Y Sawai, CA Gardine,ME Fisfalen ME .2000. CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. Journal of Immunology. 165(11): 6606-6611.
Lee CS, YJ Lee .and HF Liu .2003. Association of CTLA-4 gene A-G polymorphism with rheumatoid arthritis in Chinese. Clinical Rheumatology. (22): 221- 224
Lo B and UM Abdel-Motal. 2017..Lessons from CTLA-4 deficiency and checkpoint inhibition. Curr Opin Immunol. (49): 14-19.
MacGregor AJ, H Snieder, AS Rigby and et al. 2000. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheumatic. (43): 30-37
Meggyes M, J Szanto, A Lajko, B Farkas and et al. 2018. The possible role of CD8+/Va7.2+/CD161++ T (MAIT) and CD8+/Va7.2+/CD161 lo T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia. American Journal of Reproductive Immunology. 79:e12805.
Miko, E., M Meggyes, , K .Doba., A. Barakonyi,. and L. Szereday.2019. Immune Checkpoint Molecules in Reproductive Immunology. Frontiers in immunology. 10: 846.
Oaks MK, KM Hallett ,RT Penwell and et al.2000. A native soluble form of CTLA-4. Cell Immunology. (201): 144- 153
Okada Y, D Wu, G Trynka and et al.2014. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. (506): 376-381
Okada Y, S Eyre ,A Suzuki , Y Kochi and et al. 2019.Genetics of rheumatoid arthritis: 2018 status. Annals of the Rheumatic Diseases. Annals of Rheumatic Diseases. 78(4): 446-453
Orozco G, B Torres, A Núñez-Roldán, MF González-Escribano and J Martín.2004. Cytotoxic T-lymphocyte antigen-4-CT60 polymorphism in rheumatoid arthritis. Tissue Antigens. 64(6): 667-670.
OrrÚ S, N OrrÚ, E. Manolakos, R. Littera and et al.2012. Recipient CTLA-4*CT60-AA genotype is a prognostic factor for acute graft-versus-host disease in hematopoietic stem cell transplantation for thalassemia. Human Immunology. 73: 282-286
Saleh HM, N. Rohowsky and M. Leski.2008. The CTLA4 -819 C/T and +49 A/G dimorphisms are associated with Type 1 diabetes in Egyptian children. Indian J Human Genetics. 14(3): 92-98. doi: 10.4103/0971-6866.45001
Smolen JS, D. Aletaha, A. Barton and et al.2018. Rheumatoid arthritis. Natural Reviews in Diseases Primers 4: 18001
Tang G, H. Xie, L. Xu, Y. Hao, D. Lin and D. Ren.2002. Genetic study of apolipoprotein E gene, alpha-1 antichymotrypsin gene in sporadic parkinson disease. Am J Med Genet. (114): 446- 449.
Tsukahara S, T. Iwamoto, K. Ikari and et al.2008. CTLA-4 CT60 polymorphism is not an independent genetic risk marker of rheumatoid arthritis in a Japanese population. Annals of the Rheumatic Diseases. 67: 428-429
Vaidya B, SH. Pearce, S. Charlton and et al.2002. An association between the CTLA-4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies. Rheumatology (Oxford) (41): 1213
Vanessa MH, W.Ying, O Jan and et al. 1999. Improvements in gel composition and electrophoretic conditions for broad-range mutation analysis by denaturing gradient gel electrophoresis. Nucleic Acids Research. 27: e29
Walker LSK and DM Sansom. 2015. Confusing signals: recent progress in CTLA-4 biology. Trends in Immunology. (36): 63-70.
Walker LSK. 2017. EFIS lecture understanding the CTLA-4 checkpoint in the maintenance of immune homeostasis. Immunology Letters. (184): 43-50.
Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007; 447: 661-678
Ying Wu, VW Hayes, Osinga Jan and et al.1998. Improvement of fragment and primer selection for mutation detection by denaturing gradient gel electrophoresis. Nucleic acids Res. (26): 5432-5440
Zaletel K, B. Krhin, S. Gaberscek, A. Bicek A, T Pajic, S. Hojker.2010. Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto's and postpartum thyroiditis. Clin Exp Immunol. 1;161(1):41-7.
Zhou C, S. Gao, Z. Shu, S. Li and et al. 2020. Association between CTLA-4 Gene Polymorphism and Risk of Rheumatoid Arthritis (RA): Evidence from a Meta-analysis Involving 21681 Cases and 23457 Controls.
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