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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease that predominantly affects women. Previous findings that duplicated Toll-like receptor 7 (Tlr7) promotes lupus-like disease in male BXSB mice prompted us to evaluate TLR7 in human SLE. By using a candidate gene approach, we identified and replicated association of a TLR7 3'UTR SNP, rs3853839 (G/C), with SLE in 9,274 Eastern Asians (P(combined) = 6.5 x 10(-10)), with a stronger effect in male than female subjects [odds ratio, male vs. female = 2.33 (95% CI = 1.64-3.30) vs. 1.24 (95% CI = 1.14-1.34); P = 4.1 x 10(-4)]. G-allele carriers had increased TLR7 transcripts and more pronounced IFN signature than C-allele carriers; heterozygotes had 2.7-fold higher transcripts of G-allele than C-allele. These data established a functional polymorphism in type I IFN pathway gene TLR7 predisposing to SLE, especially in Chinese and Japanese male subjects.[1]


  1. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Shen, N., Fu, Q., Deng, Y., Qian, X., Zhao, J., Kaufman, K.M., Wu, Y.L., Yu, C.Y., Tang, Y., Chen, J.Y., Yang, W., Wong, M., Kawasaki, A., Tsuchiya, N., Sumida, T., Kawaguchi, Y., Howe, H.S., Mok, M.Y., Bang, S.Y., Liu, F.L., Chang, D.M., Takasaki, Y., Hashimoto, H., Harley, J.B., Guthridge, J.M., Grossman, J.M., Cantor, R.M., Song, Y.W., Bae, S.C., Chen, S., Hahn, B.H., Lau, Y.L., Tsao, B.P. Proc. Natl. Acad. Sci. U.S.A. (2010) [Pubmed]
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