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

• DOI: 10.1073/pnas.1001337107
• Publication Date: 2010-08-24T02:58:59Z
• Authors: Nan Shen; Qiong Fu; Yun Deng; Xiaoxia Qian; Jian Zhao; Kenneth M. Kaufman; Yee Ling Wu; C. Yung Yu; Yuanjia Tang; Ji-Yih Chen; Wanling Yang; Maida Wong; Aya Kawasaki; Naoyuki Tsuchiya; Takayuki Sumida; Yasushi Kawaguchi; Hwee Siew Howe; Mo Yin Mok; So-Young Bang; Fei-Lan Liu; Deh-Ming Chang; Yoshinari Takasaki; Hiroshi Hashimoto; John B. Harley; Joel M. Guthridge; Jennifer M. Grossman; Rita M. Cantor; Yeong Wook Song; Sang-Cheol Bae; Shunle Chen; Bevra H. Hahn; Yu Lung Lau; Betty P. Tsao
• Keywords: TLR7; SNP

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