Main Article Content
meta-analysis, TBX21, polymorphism, autoimmune diseases
Objective: To systematically evaluate the association between TBX21 gene polymorphisms (rs17250932, rs2240017, and rs4794067) and the risk of autoimmune diseases in Asian populations.
Methods: The Medline, Web of Science, and Chinese Biomedical Literature Database were used to retrieve eligible studies that were published before July 2020. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by using the dominant model, heterozygote contrast model, and allelic contrast model. Publication bias was evaluated using contour-enhanced funnel plots and Egger’s regression test. Sensitivity analysis was conducted to assess the robustness of this meta-analysis.
Results: A total of 12 eligible studies including 3834 patients and 4824 healthy controls were recruited in this meta-analysis. The pooled data demonstrated that TBX21 rs2240017 and rs4794067 polymorphisms are significantly associated with the risk of autoimmune diseases in Asian populations in allelic contrast model (OR: 1.456, 95% CI: 1.131–1.875, p=0.004; OR: 0.766, 95% CI: 0.615–0.954, p=0.017), heterozygote comparison model (OR: 1.647, 95% CI: 1.239–2.189, p=0.001; OR: 0.796, 95% CI: 0.634–0.999, p=0.049), and dominant mode (OR: 1.572, 95% CI: 1.194–2.071, p=0.004; OR: 0.767, 95% CI: 0.607–0.970, p=0.027). The G allele of rs2240017 may be a risk factor for autoimmune diseases and the T allele of rs4794067 may increase the risk of autoimmune diseases. However, we failed to find evidence of the association between TBX21 rs17250932 polymorphism and susceptibility to autoimmune diseases. No publication bias was found in this meta-analysis.
Conclusions: This meta-analysis indicated that TBX21 rs2240017 and rs4794067 polymorphisms confer susceptibility to autoimmune diseases, but not rs17250932.
2. Fazal SA, Khan M, Nishi SE, Alam F, Zarin N, Bari MT, et al. A clinical update and global economic burden of rheumatoid arthritis. Endocr Metab Immune Disord Drug Targets. 2018;18(2):98–109. http://dx.doi.org/10.2174/1871530317666171114122417
3. Farh KK-H, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 2015;518(7539):337–343. http://dx.doi.org/10.1038/nature13835
4. Lettre G, Rioux JD. Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet. 2008;17(2):R116–R121. http://dx.doi.org/10.1093/hmg/ddn246
5. Peng SL. The T-box transcription factor T-bet in immunity and autoimmunity. Cell Mol Immunol. 2006;3(2):87–95. PMID: 16696895
6. Ji N, Sosa RA, Forsthuber TG. More than just a T-box: the role of T-bet as a possible biomarker and therapeutic target in autoimmune diseases. Immunotherapy. 2011;3(3):435–441. http://dx.doi.org/10.2217/imt.10.111
7. Dardalhon V, Korn T, Kuchroo VK, Anderson AC. Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun. 2008;31(3):252–256. http://dx.doi.org/10.1016/j.jaut.2008.04.017
8. Kondo Y, Iizuka M, Wakamatsu E, Yao Z, Tahara M, Tsuboi H, et al. Overexpression of T-bet gene regulates murine autoimmune arthritis. Arthritis Rheum. 2012;64(1):162–172. http://dx.doi.org/10.1002/art.33335
9. Juedes AE, Rodrigo E, Togher L, Glimcher LH, von Herrath MG. T-bet controls autoaggressive CD8 lymphocyte responses in type I diabetes. J Exp Med. 2004;199(8):1153–1162. http://dx.doi.org/10.1084/jem.20031873
10. Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW, Marrack P. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J Clin Invest. 2017;127(4):1392–1404. http://dx.doi.org/10.1172/JCI91250
11. Morita M, Watanabe M, Inoue N, Inaoka C, Akamizu T, Tatsumi K-I, et al. Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves’ disease. Autoimmunity. 2012;45(2):129–136. http://dx.doi.org/10.3109/08916934.2011.622013
12. Leng R-X, Pan H-F, Liu J, Yang X-K, Zhang C, Tao S-S, et al. Evidence for genetic association of TBX21 and IFNG with systemic lupus erythematosus in a Chinese Han population. Sci Rep. 2016;6:22081. http://dx.doi.org/10.1038/srep22081
13. You Y, Zhao W, Chen S, Tan W, Dan Y, Hao F, et al. Association of TBX21 gene haplotypes in a Chinese population with systemic lupus erythematosus. Scand J Rheumatol. 2010;39(3):254–258. http://dx.doi.org/10.3109/03009740903347983
14. Chae SC, Shim SC, Chung HT. Association of TBX21 polymorphisms in a Korean population with rheumatoid arthritis. Exp Mol Med. 2009;41(1):33–41. http://dx.doi.org/10.3858/emm.2009.41.1.005
15. Sasaki Y, Ihara K, Matsuura N, Kohno H, Nagafuchi S, Kuromaru R, et al. Identification of a novel type 1 diabetes susceptibility gene, T-bet. Hum Genet. 2004;115(3):177–184. http://dx.doi.org/10.1007/s00439-004-1146-2
16. Liao D, Hou S, Zhang J, Fang J, Liu Y, Bai L, et al. Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and susceptibility to Behcet’s disease and Vogt-Koyanagi-Harada syndrome. Sci Rep. 2015;5:9511. http://dx.doi.org/10.1038/srep09511
17. Chen S, Zhao W, Tan W, Luo X, Dan Y, You Z, et al. Association of TBX21 promoter polymorphisms with type 1 autoimmune hepatitis in a Chinese population. Hum Immunol. 2011;72(1):69–73. http://dx.doi.org/10.1016/j.humimm.2010.10.019
18. Wang H, Yuan F-F, Dai Z-W, Wang B, Ye D-Q. Association between rheumatoid arthritis and genetic variants of natural resistance-associated macrophage protein 1 gene: a meta-analysis.Int J Rheum Dis. 2018;21(9):1651–1658. https://doi.org/10.1111/1756-185X.13366
19. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol. 2008;61(10):991–996. http://dx.doi.org/10.1016/j.jclinepi.2007.11.010
20. Mackay IR. Clustering and commonalities among autoimmune diseases. J Autoimmun. 2009;33(3–4, SI):170–177. http://dx.doi.org/10.1016/j.jaut.2009.09.006
21. Goodnow CC, Sprent J, Fazekas de St Groth B, Vinuesa CG. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature. 2005;435(7042):590–597. http://dx.doi.org/10.1038/nature03724
22. Bentham J, Morris DL, Graham DSC, Pinder CL, Tombleson P, Behrens TW, et al. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus. Nat Genet. 2015;47(12):1457–1464. http://dx.doi.org/10.1038/ng.3434
23. Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010;42(6):508–556. http://dx.doi.org/10.1038/ng.582
24. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine. 2015;74(1):5–17. http://dx.doi.org/10.1016/j.cyto.2014.09.011
25. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. J Immunol. 2015;194(7):2961–2975. http://dx.doi.org/10.1016/s0092-8674(00)80702-3
26. Lugo-Villarino G, Maldonado-Lopez R, Possemato R, Penaranda C, Glimcher LH. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells. Proc Natl Acad Sci USA. 2003;100(13):7749–7754. http://dx.doi.org/10.1073/pnas.1332767100
27. Li J-R, Li J-G, Deng G-H, Zhao W-L, Dan Y-J, Wang Y-M, et al. A common promoter variant of TBX21 is associated with allele specific binding to Yin-Yang 1 and reduced gene expression. Scand J Immunol. 2011;73(5):449–458. http://dx.doi.org/10.1111/j.1365-3083.2011.02520.x