| Literature DB >> 20733074 |
Nan Shen1, 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.
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.Entities:
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Year: 2010 PMID： 20733074 PMCID： PMC2936646 DOI： 10.1073/pnas.1001337107
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205