Synergetic Interaction of HLA-DRB1*07 Allele and TNF-Alpha − 863 C/A Single Nucleotide Polymorphism in the Susceptibility to Systemic Lupus Erythematosus
Tóm tắt
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-α) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-α gene promoter region (from − 250 to − 1000 base pairs) was analyzed by direct Sanger’s DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-α genetic polymorphisms including, − 863C/A (rs1800630), − 857C/T (rs1799724), − 806C/T (rs4248158), − 646G/A (rs4248160), − 572A/C (rs4248161) and − 308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-α gene promoter SNPs with SLE patients. However, the − 863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04–2.53, P = 0.034). We found serum TNF-α level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-α alleles at positions − 863C, − 857C, − 806C, − 646G, − 572A and − 308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35–0.82, P = 0.004). Additionally, the TNF-α − 863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73–13.29, P = 0.0009). In conclusion, TNF-α − 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α − 863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.
Tài liệu tham khảo
Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110–21.
Sun KH, Yu CL, Tang SJ, Sun GH. Monoclonal anti-double-stranded DNA autoantibody stimulates the expression and release of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha from normal human mononuclear cells involving in the lupus pathogenesis. Immunology. 2000;99:352–60.
Tucci M, Stucci S, Strippoli S, Silvestris F. Cytokine overproduction, T-cell activation, and defective T-regulatory functions promote nephritis in systemic lupus erythematosus. J Biomed Biotechnol. 2010. https://doi.org/10.1155/2010/457146.
Aringerv M, Smolen JS. Cytokine expression in lupus kidneys. Lupus. 2005;14:13–8.
Adhya Z, Borozdenkova S, Karim MY. The role of cytokines as biomarkers in systemic lupus erythematosus and lupus nephritis. Nephrol Dial Transplant. 2011;26:3273–80.
Smolen JS, Steiner G, Aringer M. Anti-cytokine therapy in systemic lupus erythematosus. Lupus. 2005;14:189–91.
MacEwan DJ. TNF ligands and receptors—a matter of life and death. Br J Pharmacol. 2002;135:855–75.
McDevitt H, Munson S, Ettinger R, Wu A. Multiple roles for tumor necrosis factor-alpha and lymphotoxin alpha/beta in immunity and autoimmunity. Arthritis Res. 2002;4:S141–52.
Vandenabeele P, Declercq W, Beyaert R, Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 1995;5:392–9.
Charles P, Elliott MJ, Davis D, Potter A, Kalden JR, Antoni C, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. J Immunol. 1999;163:1521–8.
Boswell JM, Yui MA, Burt DW, Kelley VE. Increased tumor necrosis factor and IL-1 beta gene expression in the kidneys of mice with lupus nephritis. J Immunol. 1998;141:3050–4.
Brennan DC, Yui MA, Wuthrich RP, Kelley VE. Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. J Immunol. 1989;143:3470–5.
Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, et al. Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985;13:6361–73.
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA. 1997;94:3195–9.
Katkam SK, Rajasekhar L, Kutala VK. The influence of functional polymorphic positions of HLA-DRβ1 molecules on risk for South Indian systemic lupus erythematosus patients. Lupus. 2018;27:991–1000.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.
Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 2005;15:97–8.
Postal M, Appenzeller S. The role of Tumor Necrosis Factor-alpha (TNF-α) in the pathogenesis of systemic lupus erythematosus. Cytokine. 2011;56:537–43.
Studnicka-Benke A, Steiner G, Petera P, Smolen JS. Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol. 1996;35:1067–74.
Gabay C, Cakir N, Moral F, Roux-Lombard P, Meyer O, Dayer JM, et al. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol. 1997;24:303–8.
Zhu LJ, Landolt-Marticorena C, Li T, Yang X, Yu XQ, Gladman DD, et al. Altered expression of TNF-alpha signaling pathway proteins in systemic lupus erythematosus. J Rheumatol. 2010;37:1658–66.
Gómez D, Correa PA, Gómez LM, Cadena J, Molina JF, Anaya JM. Th1/Th2 cytokines in patients with systemic lupus erythematosus: Is tumor necrosis factor alpha protective? Semin Arthritis Rheum. 2004;33:404–13.
Hohjoh H, Tokunaga K. Allele-specific binding of the ubiquitous transcription factor OCT-1 to the functional single nucleotide polymorphism (SNP) sites in the tumor necrosis factor-alpha gene (TNFA) promoter. Genes Immun. 2001;2:105–9.
Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol. 1997;34:391–9.
Katkam SK, Kumaraswami K, Rupasree Y, Thishya K, Rajasekhar L, Kutala VK. Association of CTLA4 exon-1 polymorphism with the tumor necrosis factor-α in the risk of systemic lupus erythematosus among South Indians. Hum Immunol. 2016;77:158–64.
Umare VD, Pradhan VD, Rajadhyaksha AG, Patwardhan MM, Ghosh K, Nadkarni AH. Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients. Hum Immunol. 2017;78(2):201–8.
Angelo HD, da Silva HA, Asano NM, Muniz MT, de Mascena Diniz Maia M, deSouza PR. Tumor necrosis factor alpha promoter polymorphism − 308 G/A in Brazilian patients with systemic lupus erythematosus. Hum Immunol. 2012;73:1166–70.
Sullivan KE, Wooten C, Schmeckpeper BJ, Goldman D, Petri MA. A promoter polymorphism of tumor necrosis factor alpha associated with systemic lupus erythematosus in African-Americans. Arthritis Rheum. 1997;40:2207–11.
Dourmishev L, Kamenarska Z, Hristova M, Dodova R, Kaneva R, Mitev V. Association of TNF-α polymorphisms with adult dermatomyositis and systemic lupus erythematosus in Bulgarian patients. Int J Dermatol. 2012;51:1467–73.
Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L, et al. Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens. 2007;70:376–82.
Tobón GJ, Correa PA, Gomez LM, Anaya JM. Lack of association between TNF-308 polymorphism and the clinical and immunological characteristics of systemic lupus erythematosus and primary Sjögren’s syndrome. Clin Exp Rheumatol. 2005;23:339–44.
Zúñiga J, Vargas-Alarcón G, Hernández-Pacheco G, Portal-Celhay C, Yamamoto-Furusho JK, Granados J. Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with systemic lupus erythematosus (SLE). Genes Immun. 2001;2:363–6.
van der Linden MW, van der Slik AR, Zanelli E, Giphart MJ, Pieterman E, Schreuder GM, et al. Six microsatellite markers on the short arm of chromosome 6 in relation to HLA-DR3 and TNF-308A in systemic lupus erythematosus. Genes Immun. 2001;2:373–80.
Suárez A, López P, Mozo L, Gutiérrez C. Differential effect of IL10 and TNF alpha genotypes on determining susceptibility to discoid and systemic lupus erythematosus. Ann Rheum Dis. 2005;64:1605–10.
Santos MJ, Carmona-Fernandes D, Caetano-Lopes J, Perpétuo IP, Vidal B, Capela S, et al. TNF promoter − 308 G > A and LTA 252 A > G polymorphisms in Portuguese patients with systemic lupus erythematosus. Rheumatol Int. 2012;32:2239–44.
Lin YJ, Chen RH, Wan L, Sheu JC, Huang CM, Lin CW, et al. Association of TNF-alpha gene polymorphisms with systemic lupus erythematosus in Taiwanese patients. Lupus. 2009;18:974–9.
Lin YJ, Wan L, Huang CM, Sheu JJ, Chen SY, Lin TH, et al. IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. Clin Exp Rheumatol. 2010;28:318–24.
Pan HF, Leng RX, Wang C, Qin WZ, Chen LL, Zha ZQ, et al. Association of TNF-α promoter-308 A/G polymorphism with susceptibility to systemic lupus erythematosus: a meta-analysis. Rheumatol Int. 2012;32:2083–92.
Lee YH, Harley JB, Nath SK. Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet. 2006;14:364–71.
Chen L, Huang Z, Liao Y, Yang B, Zhang J. Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis. Braz J Med Biol Res. 2019;52(3):e7927.
Farid TM, AbdElBaky AM, Khalefa ES, Talaat AA, Mohamed AA, Gheita TA, et al. Association of tumor necrosis factor-alpha gene polymorphisms with juvenile systemic lupus erythematosus nephritis in a cohort of Egyptian patients. Iran J Kidney Dis. 2011;5:392–7.
Gordon C, Ranges GE, Greenspan JS, Wofsy D. Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice. Clin Immunol Immunopathol. 1989;52:421–34.
Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med. 1983;177:557–60.
Agrawal S, Srivastava SK, Borkar M, Chaudhuri TK. Genetic affinities of north and northeastern populations of India: inference from HLA-based study. Tissue Antigens. 2008;72:120–30.
Shanmugalakshmi S, Balakrishnan K, Manoharan K, Pitchappan RM. HLA-DRB1*,-DQB1* in Piramalai Kallars and Yadhavas, two Dravidian-speaking castes of Tamil Nadu, South India. Tissue Antigens. 2003;61:451–64.
Bendtzen K, Morling N, Fomsgaard A, Svenson M, Jakobsen B, Odum N, et al. Association between HLA-DR2 and production of tumour necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide. Scand J Immunol. 1988;28:599–606.
Jacob CO, Fronek Z, Lewis GD, Koo M, Hansen JA, McDevitt HO. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA. 1990;87:1233–7.
Pociot F, Briant L, Jongeneel CV, Mölvig J, Worsaae H, Abbal M, et al. Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol. 1993;23:224–31.
Fletcher GJ, Samuel P, Christdas J, Gnanamony M, Ismail AM, Anantharam R, et al. Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population. Genes Immun. 2011;12:552–8.
Alagarasu K, Mulay AP, Singh R, Gavade VB, Shah PS, Cecilia D. Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever. Hum Immunol. 2013;74:610–7.