Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosusopen access
- Authors
- Shen, Nan; Fu, Qiong; Deng, Yun; Qian, Xiaoxia; Zhao, Jian; Kaufman, Kenneth M.; Wu, Yee Ling; Yu, C. Yung; Tang, Yuanjia; Chen, Ji-Yih; Yang, Wanling; Wong, Maida; Kawasaki, Aya; Tsuchiya, Naoyuki; Sumida, Takayuki; Kawaguchi, Yasushi; Howe, Hwee Siew; Mok, Mo Yin; Bang, So-Young; Liu, Fei-Lan; Chang, Deh-Ming; Takasaki, Yoshinari; Hashimoto, Hiroshi; Harley, John B.; Guthridge, Joel M.; Grossman, Jennifer M.; Cantor, Rita M.; Song, Yeong Wook; Bae, Sang-Cheol; Chen, Shunle; Hahn, Bevra H.; Lau, Yu Lung; Tsao, Betty P.
- Issue Date
- Sep-2010
- Publisher
- NATL ACAD SCIENCES
- Keywords
- functional polymorphism; disease susceptibility; autoimmunity; type I interferon
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.36, pp.15838 - 15843
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 107
- Number
- 36
- Start Page
- 15838
- End Page
- 15843
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/174217
- DOI
- 10.1073/pnas.1001337107
- ISSN
- 0027-8424
- Abstract
- 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.
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