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Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15838-43. doi: 10.1073/pnas.1001337107. Epub 2010 Aug 23.

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

Author information

  • 1Shanghai Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China. nanshensibs@gmail.com

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.

PMID:
20733074
[PubMed - indexed for MEDLINE]
PMCID:
PMC2936646
Free PMC Article

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