Abstract
T cell activation participates in the pathogenesis of rheumatoid arthritis (RA), and the signaling molecule zeta-chain-associated protein kinase 70 kDa (ZAP-70) plays a crucial role in this process. Different mutations in the coding sequence of ZAP-70 are involved in a variety of immunological phenotypes, and recent evidence indicates that genetic variations within the 3′ untranslated regions (UTR) of microRNA binding sites may affect the hybridization with target mRNAs, leading to phenotype changes with disease status. In this study, we evaluated the possible effect of ZAP-70 polymorphism as a genetic risk factor in RA by examining the single-nucleotide polymorphism in 100 patients and 100 ethnicity- and sex-matched healthy individuals from southern Taiwan. In both groups, the genotype distribution of rs2278699 in the 3′ UTR was in the Hardy-Weinberg equilibrium. In RA, there were higher frequencies of the G allele (15.5 versus 8.0 %, odds ratio 2.1, P = 0.020) and significant differences in the trend of various genotypes (P = 0.024). The results suggest that genetic polymorphism in the 3′ UTR of ZAP-70 is associated with RA susceptibility in southern Taiwanese.
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References
Au-Yeung BB, Deindl S, Hsu LY, Palacios EH, Levin SE, Kuriyan J, Weiss A (2009) The structure, regulation, and function of ZAP-70. Immunol Rev 228:41–57
Wang CR, Liu MF (2003) Regulation of CCR5 expression and MIP-1alpha production in CD4+ T cells from patients with rheumatoid arthritis. Clin Exp Immunol 132:371–378
McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219
Caporali R, Bugatti S, Cavagna L, Antivalle M, Sarzi-Puttini P (2014) Modulating the co-stimulatory signal for T cell activation in rheumatoid arthritis: could it be the first step of the treatment? Autoimmune Rev 13:49–53
Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, Sakihama T, Matsutani T, Negishi I, Nakatsuru S et al (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426:454–460
Wang CR, Guo HR, Liu MF (2005) RANTES promoter polymorphism as a genetic risk factor for rheumatoid arthritis in the Chinese. Clin Exp Rheumatol 23:379–384
Nambiar MP, Enyedy EJ, Warke VG, Krishnan S, Dennis G, Wong HK, Kammer GM, Tsokos GC (2001) T cell signaling abnormalities in systemic lupus erythematosus are associated with increased mutations/polymorphisms and splice variants of T cell receptor zeta chain messenger RNA. Arthritis Rheum 44:1336–1350
Wang H, Kadlecek TA, Au-Yeung BB, Goodfellow HE, Hsu LY, Freedman TS, Weiss A (2010) ZAP-70: an essential kinase in T-cell signaling. Cold Spring Harb Perspect Biol 2:a002279
Liu C, Rennie WA, Carmack CS, Kanoria S, Cheng J, Lu J, Ding Y (2014) Effects of genetic variations on microRNA: target interactions. Nucleic Acid Res 42:9543–9552
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581
Buckley C, Douek D, Newsom-Davis J, Vincent A, Willcox N (2001) Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 50:64–72
Koetz K, Bryl E, Spickschen K, O’Fallon WM, Goronzy JJ, Weyand CM (2000) T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA 97:9203–9208
Duroux-Richard I, Jorgensen C, Apparailly F (2012) What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum 64:11–20
Hill CG, Jabbari N, Matyunina LV, McDonald JF (2014) Functional and evolutionary significance of human microRNA seed region mutations. PLoS One 9:e115241
Zizzo G, De Santis M, Bosello SL, Fedele AL, Peluso G, Gremese E, Tolusso B, Ferraccioli G (2011) Synovial fluid-derived T helper 17 cells correlate with inflammatory activity in arthritis, irrespectively of diagnosis. Clin Immunol 138:107–116
Acknowledgments
This work was supported by grants NSC 91-2314-B-019, 92-2314-B-006-047, and MOST 103-2314-B-006-058-MY3 from the Ministry of Science and Technology, Taiwan, Republic of China.
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Chen, SY., Liu, MF. & Wang, CR. Genetic polymorphism of 3′ untranslated region of zeta-chain associated protein kinase 70 kDa in southern Taiwanese patients with rheumatoid arthritis. Clin Rheumatol 35, 747–750 (2016). https://doi.org/10.1007/s10067-015-3044-5
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DOI: https://doi.org/10.1007/s10067-015-3044-5