title: Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus.
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.
authors: Shanghai Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China. nanshensibs@gmail.com
authors: Nan
authors: N
authors: Shen
authors: Qiong
authors: Q
authors: Fu
authors: Yun
authors: Y
authors: Deng
authors: Xiaoxia
authors: X
authors: Qian
authors: Jian
authors: J
authors: Zhao
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Yee Ling
authors: YL
authors: Wu
authors: C Yung
authors: CY
authors: Yu
authors: Yuanjia
authors: Y
authors: Tang
authors: Ji-Yih
authors: JY
authors: Chen
authors: Wanling
authors: W
authors: Yang
authors: Maida
authors: M
authors: Wong
authors: Aya
authors: A
authors: Kawasaki
authors: Naoyuki
authors: N
authors: Tsuchiya
authors: Takayuki
authors: T
authors: Sumida
authors: Yasushi
authors: Y
authors: Kawaguchi
authors: Hwee Siew
authors: HS
authors: Howe
authors: Mo Yin
authors: MY
authors: Mok
authors: So-Young
authors: SY
authors: Bang
authors: Fei-Lan
authors: FL
authors: Liu
authors: Deh-Ming
authors: DM
authors: Chang
authors: Yoshinari
authors: Y
authors: Takasaki
authors: Hiroshi
authors: H
authors: Hashimoto
authors: John B
authors: JB
authors: Harley
authors: Joel M
authors: JM
authors: Guthridge
authors: Jennifer M
authors: JM
authors: Grossman
authors: Rita M
authors: RM
authors: Cantor
authors: Yeong Wook
authors: YW
authors: Song
authors: Sang-Cheol
authors: SC
authors: Bae
authors: Shunle
authors: S
authors: Chen
authors: Bevra H
authors: BH
authors: Hahn
authors: Yu Lung
authors: YL
authors: Lau
authors: Betty P
authors: BP
authors: Tsao
mesh_terms: D000483:Alleles; D044466:Asian People; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012737:Sex Factors; D051199:Toll-Like Receptor 7 / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7