Summary
B and T lymphocyte attenuator (BTLA) is an immuno-inhibitory receptor with the ability to deliver inhibitory signal for suppressing lymphocyte activation. To test the potential association of the human BTLA gene with the development of rheumatoid arthritis (RA), a genetic case-control association study was conducted, by using a single nucleotide polymorphism (SNP), C+800T SNP, in the exon 5 of the human BTLA gene for genotyping 93 RA patients and 294 normal control individuals. The results showed that there is statistically significant difference in the genotype distributions between RA and control groups (p = 0.022). When compared with the heterozygous genotype (C/T genotype), the homozygous genotype (C/C or T/T genotype) appears to confer the increased risk of the RA susceptibility with the odds ratio of 1.88 (p = 0.015). These data indicate the significant association between the C+800T SNP in the BTLA gene with the RA susceptibility.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Riley J.L., June C.H. (2005). The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation. Blood 105: 13–21
Greenwald R.J., Freeman G.J., Sharpe A.H. (2005). The B7 Family Revisited. Annu. Rev. Immunol. 23: 515–548
Nishimura H., Minato N., Nakano T., Honjo T. (1998). Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int. Immunol. 10: 1563–1572
Watanabe N., Gavrieli M., Sedy J.R., Yang J., Fallarino F., Loftin S.K., Hurchla M.A., Zimmerman N., Sim J., Zang X., Murphy T.L., Russell J.H., Allison J.P., Murphy K.M. (2003), BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat. Immunol. 4: 670–679
Han P., Goularte O.D., Rufner K., Wilkinson B., Kaye J. (2004) An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. J. Immunol. 172: 5931–5939
Shahinian A., Pfeffer K., Lee K.P., Kundig T.M., Kishihara K., Wakeham A., Kawai K., Ohashi P.S., Thompson C.B., Mak T.W. (1993) Differential T cell costimulatory requirements in CD28-deficient mice. Science 261: 609–612
Dong C., Juedes A.E., Temann U.A., Shresta S., Allison J.P., Ruddle N.H., Flavell R.A. (2001) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409: 97–101
Tivol E.A., Borriello F., Schweitzer A.N., Lynch W.P., Bluestone J.A., Sharpe A.H. (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3: 541–547
Nishimura H., Nose M., Hiai H., Minato N., Honjo T. (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11: 141–151
Nishimura H., Okazaki T., Tanaka Y., Nakatani K., Hara M., Matsumori A., Sasayama S., Mizoguchi A., Hiai H., Minato N., Honjo T. (2001) Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291: 319–322
Sedy J.R., Gavrieli M., Potter K.G., Hurchla M.A., Lindsley R.C., Hildner K., Scheu S., Pfeffer K., Ware C.F., Murphy T.L., Murphy K.M. (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol 6: 90–98
Gonzalez L.C., Loyet K.M., Calemine-Fenaux J., Chauhan V., Wranik B., Ouyang W., Eaton D.L. (2005) A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Proc. Natl. Acad. Sci. USA 102:1116–1121
Wang Y., Subudhi S.K., Anders R.A., Lo J., Sun Y., Blink S., Wang Y., Wang J., Liu X., Mink K., Degrandi D., Pfeffer K., Fu Y.X. (2005). The role of herpesvirus entry mediator as a negative regulator of T cell-mediated responses. J. Clin. Invest. 115:711–717
Kwon B.S., Tan K.B., Ni J., Oh K.O., Lee Z.H., Kim K.K., Kim Y.J., Wang S., Gentz R., Yu G.L., Harrop J., Lyn S.D., Silverman C., Porter T.G., Truneh A., Young P.R. (1997). A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation. J. Biol. Chem. 272: 14272–14276
Miltenburg A.M., van Laar J.M., de Kuiper R., Daha M.R., Breedveld F.C. (1992). T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset. Scand. J. Immunol. 35:603–610
Quayle A.J., Chomarat P., Miossec P., Kjeldsen-Kragh J., Forre O., Natvig J.B. (1993). Rheumatoid inflammatory T-cell clones express mostly Th1 but also Th2 and mixed (Th0-like) cytokine patterns. Scand. J. Immunol. 38: 75–82
Simon A.K., Seipelt E., Sieper J. (1994). Divergent T-cell cytokine patterns in inflammatory arthritis. Proc. Natl. Acad. Sci. USA 91: 8562–8566
Arnett F.C., Edworthy S.M., Bloch D.A., McShane D.J., Fries J.F., Cooper N.S., Healey L.A., Kaplan S.R., Liang M.H., Luthra H.S., Medsger T.A., Mitchell D.M., Neustadt A.H., Pinals R.S., Schaller J.G., Sharp J.T., Wilder R.L., Hunder G.G. (1988). The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis. Rheum. 31: 315–324
Stastny P. (1978). Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N. Engl. J. Med. 298:869–871
Choi S.J., Rho Y.H., Ji J.D., Song G.G., Lee Y.H. (2006). Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45:166–170
Seldin M.F., Amos C.I., Ward R., Gregersen P.K. (1999). The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum. 42:1071–1079
Oliver J.E., Worthington J., Silman A.J. (2006), Genetic epidemiology of rheumatoid arthritis. Curr. Opin. Rheumatol. 18:141–146
Dieude P., Cornelis F. (2005). Genetic basis of rheumatoid arthritis. Joint Bone Spine 72:520–526
Han S., Li Y., Mao Y., Xie Y. (2005). Meta-analysis of the association of CTLA-4 exon-1 +49A/G polymorphism with rheumatoid arthritis. Hum. Genet. 118:123–132
Prokunina L., Padyukov L., Bennet A., de Faire U., Wiman B., Prince J., Alfredsson L., Klareskog L., Alarcó n-Riquelme M. (2004). Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum. 50:1770–1773
Lin S.-C., Yen J.-H., Tsai J.-J., Tsai W.-C., Ou T.-T., Liu H.-W., Chen C.-J. (2004). Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum. 50: 770–775
Gavrieli M., Watanabe N., Loftin S., Murphy T., Murphy K. (2003). Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2. Biochem. Biophys. Res. Commun. 312: 1236–1243
Shiratori T., Miyatake S., Ohno H., Nakaseko C., Isono K., Bonifacino J.S., Saito T. (1997) Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2. Immunity 6: 583–589
Zhang Y., Allison J.P. (1997) Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. Proc. Natl. Acad. Sci. USA 94: 9273–9278
Mauri D.N., Ebner R., Montgomery R.I., Kochel K.D., Cheung T.C., Yu G.L., Ruben S., Murphy M., Eisenberg R.J., Cohen G.H., Spear P.G., Ware C.F. (1998) LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 8: 21–30
Watts T.H. (2005). TNF/TNFR family members in costimulation of T cell responses. Annu. Rev. Immunol. 23: 23–68
Fava R.A., Notidis E., Hunt J., Szanya V., Ratcliffe N., Ngam-ek A., de Fougerolles A.R., Sprague A., Browning J.L. (2003). A role for the lymphotoxin/LIGHT axis in the pathogenesis of murine collagen-induced arthritis. J. Immunol. 171: 115–126
Acknowledgements
I thank Dr Chung-Jen Chen (Chang Gung Memorial Hospital at Kaohsiung, Taiwan) and Yanfeng Lu for review of the manuscript. This project is partly supported by a grant from the National Science Council of Taiwan (Grant# 92-2314-B-281-002-).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lin, SC., Kuo, CC. & Chan, CH. Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis. J Biomed Sci 13, 853–860 (2006). https://doi.org/10.1007/s11373-006-9113-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11373-006-9113-7