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

  • Shen, Nan
  • Fu, Qiong
  • Deng, Yun
  • Qian, Xiaoxia
  • Zhao, Jian
  • ... Bang, So-Young
  • 외 27명
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초록

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.

키워드

functional polymorphismdisease susceptibilityautoimmunitytype I interferonPLASMACYTOID DENDRITIC CELLSGENOME-WIDE ASSOCIATIONDISEASE-ACTIVITYCHROMOSOME INACTIVATIONAUTOIMMUNE-DISEASESCOPY NUMBERCAG REPEATGENEVARIANTSINTERFERON
제목
Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus
저자
Shen, NanFu, QiongDeng, YunQian, XiaoxiaZhao, JianKaufman, Kenneth M.Wu, Yee LingYu, C. YungTang, YuanjiaChen, Ji-YihYang, WanlingWong, MaidaKawasaki, AyaTsuchiya, NaoyukiSumida, TakayukiKawaguchi, YasushiHowe, Hwee SiewMok, Mo YinBang, So-YoungLiu, Fei-LanChang, Deh-MingTakasaki, YoshinariHashimoto, HiroshiHarley, John B.Guthridge, Joel M.Grossman, Jennifer M.Cantor, Rita M.Song, Yeong WookBae, Sang-CheolChen, ShunleHahn, Bevra H.Lau, Yu LungTsao, Betty P.
DOI
10.1073/pnas.1001337107
발행일
2010-09
유형
Article
저널명
Proceedings of the National Academy of Sciences of the United States of America
107
36
페이지
15838 ~ 15843

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