Cytotoxic T Lymphocyte Antigen 4 Gene +49 A/G (rs231775) Polymorphism and Susceptibility to Systemic Lupus Erythematosus

Author(s): Rania Mohammed Kishk, Maii Abdelraheem Abdellatif, Raghda Elsawi Eldesouki*, Mohamed Fawzy, Shaymaa Abdelraheem Abdelhady, Marwa Mohamed Fouad

Journal Name: Current Rheumatology Reviews

Volume 17 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Abstract:

Aim: To assess the probable role of +49AG polymorphism in susceptibility to SLE in an Egyptian population.

Background: Systemic lupus erythematosus (SLE) is a compound inflammatory chronic disease distinguished through the release of autoantibodies. Cytotoxic T lymphocyte associated antigen-4 is a main down controller of T-cell response; its dysregulation could affect SLE pathogenesis by altered T cells activation to self-antigens.

Objectives: To evaluate the CTLA-4 +49AG allelic and genotype frequency in a sample of the Egyptian population and correlate them with disease susceptibility and clinical severity.

Materials and methods: Including 100 patients with SLE and 100 healthy controls (age and gender matched), CTLA-4 exon 1 49 A>G Genotyping was done using Real-Time PCR.

Results: No difference was noticed in genotype or allele distributions of the studied polymorphism between both groups. Similar genotypes and allele frequencies were established for the 2 groups after their stratification by the age of disease onset, clinical course, or severity.

Conclusion: CTLA-4 +49AG gene polymorphism is not linked with the liability to develop SLE in the studied Egyptian population. Yet it is significantly related to disease severity.

Keywords: Systemic lupus polymorphisms, CTLA-4, SNP genotyping, (rs231775), (+49 A/G), PCR.

[1]
Walunas TL, Bakker CY, Bluestone JA. CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med 1996; 183(6): 2541-50.
[http://dx.doi.org/10.1084/jem.183.6.2541] [PMID: 8676075]
[2]
Utz PJ. Multiplexed assays for identification of biomarkers and surrogate markers in systemic lupus erythematosus. Lupus 2004; 13(5): 304-11.
[http://dx.doi.org/10.1191/0961203303lu1017oa] [PMID: 15230283]
[3]
Devaraju P, Mehra S, Gulati R, et al. The IRF5 rs2004640 (G/T) polymorphism is not a genetic risk factor for systemic lupus erythematosus in population from south India. Indian J Med Res 2018; 147(6): 560-6.
[http://dx.doi.org/10.4103/ijmr.IJMR_2025_16] [PMID: 30168487]
[4]
El Guindy NM, Ghaffar HA, El Refai RM, El Hawary RE. Cytotoxic T lymphocyte antigen-4 gene polymorphism in systemic lupus erythematosus Egyptian patients. Comp Clin Pathol 2015; 24(1): 41-5.
[http://dx.doi.org/10.1007/s00580-013-1852-z]
[5]
Shojaa M, Amoli M, Aghaie M, et al. CTLA-4 polymorphism in Iranian patients with systemic lupus erythematosus. Am J Exp Clin Res 2014; 1(4): 68-71.
[PMID: 24400885]
[6]
Wakeland EK, Liu K, Graham RR, Behrens TW. Delineating the genetic basis of systemic lupus erythematosus. Immunity 2001; 15(3): 397-408.
[http://dx.doi.org/10.1016/S1074-7613(01)00201-1] [PMID: 11567630]
[7]
Harper K, Balzano C, Rouvier E, Mattéi MG, Luciani MF, Golstein P. CTLA-4 and CD28 activated lymphocyte molecules are closely related in both mouse and human as to sequence, message expression, gene structure, and chromosomal location. J Immunol 1991; 147(3): 1037-44.
[PMID: 1713603]
[8]
Kristiansen OP, Larsen ZM, Pociot F. CTLA-4 in autoimmune diseases--a general susceptibility gene to autoimmunity? Genes Immun 2000; 1(3): 170-84.
[http://dx.doi.org/10.1038/sj.gene.6363655] [PMID: 11196709]
[9]
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40(9): 1725.
[http://dx.doi.org/10.1002/art.1780400928] [PMID: 9324032]
[10]
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. The Committee on Prognosis Studies in SLE. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum 1992; 35(6): 630-40.
[http://dx.doi.org/10.1002/art.1780350606] [PMID: 1599520]
[11]
Chambers CA, Krummel MF, Boitel B, et al. The role of CTLA-4 in the regulation and initiation of T-cell responses. Immunol Rev 1996; 153(1): 27-46.
[http://dx.doi.org/10.1111/j.1600-065X.1996.tb00919.x] [PMID: 9010718]
[12]
Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423(6939): 506-11.
[http://dx.doi.org/10.1038/nature01621] [PMID: 12724780]
[13]
Yates AD, Achuthan P, Akanni W, et al. Ensembl 2020. Nucleic Acids Res 2020; 48(D1): D682-8.
[PMID: 31691826]
[14]
Kailashiya V, Sharma HB, Kailashiya J. Role of CTLA4 A49G polymorphism in systemic lupus erythematosus and its geographical distribution. J Clin Pathol 2019; 72(10): 659-62.
[http://dx.doi.org/10.1136/jclinpath-2019-206013] [PMID: 31340988]
[15]
Karabon L, Kosmaczewska A, Bilinska M, et al. The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease. Immunology 2009; 128(1)(Suppl.): e787-96.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03083.x] [PMID: 19740340]
[16]
Patel H, Mansuri MS, Singh M, Begum R, Shastri M, Misra A. Association of cytotoxic T-lymphocyte antigen 4 (CTLA4) and thyroglobulin (TG) genetic variants with autoimmune hypothyroidism. PLoS One 2016; 11(3): e0149441.
[http://dx.doi.org/10.1371/journal.pone.0149441] [PMID: 26963610]
[17]
Lin LP, Chen QY, Zhang T, Guo PF, Li DJ. The CD4+CD25 bright regulatory T cells and CTLA-4 expression in peripheral and decidual lymphocytes are down-regulated in human miscarriage. Clin Immunol 2009.
[18]
Song Y, Chen Y, Xu Q. Association among cytotoxic T-lymphocyte antigen 4 gene, rs231775 polymorphism, and recurrent pregnancy loss risk. Biosci Rep 2019; 39(2): BSR20181760.
[http://dx.doi.org/10.1042/BSR20181760] [PMID: 30578376]
[19]
Eagar TN, Karandikar NJ, Bluestone JA, Miller SD. The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance. Eur J Immunol 2002; 32(4): 972-81.
[http://dx.doi.org/10.1002/1521-4141(200204)32:4<972::AID-IMMU972>3.0.CO;2-M] [PMID: 11920563]
[20]
Chang WW, Zhang L, Yao YS, Su H. Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis. Mol Biol Rep 2012; 39(9): 9159-65.
[http://dx.doi.org/10.1007/s11033-012-1788-4] [PMID: 22718509]
[21]
Lee YH, Harley JB, Nath SK. CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis. Hum Genet 2005; 116(5): 361-7.
[http://dx.doi.org/10.1007/s00439-004-1244-1] [PMID: 15688186]
[22]
Barreto M, Santos E, Ferreira R, et al. Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus. Eur J Hum Genet 2004; 12(8): 620-6.
[http://dx.doi.org/10.1038/sj.ejhg.5201214] [PMID: 15138458]
[23]
Gunesacar R, Erken E, Bozkurt B, et al. Analysis of CD28 and CTLA-4 gene polymorphisms in Turkish patients with Behcet’s disease. Int J Immunogenet 2007; 34(1): 45-9.
[http://dx.doi.org/10.1111/j.1744-313X.2007.00655.x] [PMID: 17284227]
[24]
Ahmed S, Ihara K, Kanemitsu S, et al. Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population. Rheumatology (Oxford) 2001; 40(6): 662-7.
[http://dx.doi.org/10.1093/rheumatology/40.6.662] [PMID: 11426024]
[25]
Mahdieh S, Mahsa MA, Mehrdad A. etal. CTLA-4 polymorphism in Iranian patients with systemic lupus erythematosus. Am J Exp Clin Res 2014; 1(4): 68-71.
[26]
Elshazli R, Settin A, Salama A. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) +49 A>G gene polymorphism in Egyptian cases with rheumatoid arthritis. Gene 2015; 558(1): 103-7.
[http://dx.doi.org/10.1016/j.gene.2014.12.046] [PMID: 25542810]
[27]
Sugimoto K, Fujita S, Yanagida H, et al. Clinical manifestations and analyses of the cytotoxic T-lymphocyte associated-4 gene in two Japanese families with systemic lupus erythematosus. Clin Exp Nephrol 2008; 12(2): 149-54.
[http://dx.doi.org/10.1007/s10157-007-0019-0] [PMID: 18185908]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2021
Published on: 19 November, 2020
Page: [247 - 251]
Pages: 5
DOI: 10.2174/1573397116666201119145153
Price: $65

Article Metrics

PDF: 48
HTML: 2