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

Proceedings of the National Academy of Sciences - PNAS, 2010-09, Vol.107 (36), p.15838-15843 [Peer Reviewed Journal]

Copyright © 1993-2008 The National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Sep 7, 2010 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1001337107 ;PMID: 20733074

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Title:
Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus
Author: Shen, Nan ; Fu, Qiong ; Deng, Yun ; Qian, Xiaoxia ; Zhao, Jian ; Kaufman, Kenneth M. ; Wu, Yee Ling ; Yu, C. Yung ; Tang, Yuanjia ; Chen, Ji-Yih ; Yang, Wanling ; Wong, Maida ; Kawasaki, Aya ; Tsuchiya, Naoyuki ; Sumida, Takayuki ; Kawaguchi, Yasushi ; Howe, Hwee Siew ; Mok, Mo Yin ; Bang, So-Young ; Liu, Fei-Lan ; Chang, Deh-Ming ; Takasaki, Yoshinari ; Hashimoto, Hiroshi ; Harley, John B. ; Guthridge, Joel M. ; Grossman, Jennifer M. ; Cantor, Rita M. ; Song, Yeong Wook ; Bae, Sang-Cheol ; Chen, Shunle ; Hahn, Bevra H. ; Lau, Yu Lung ; Tsao, Betty P. ; Smith, Kenneth G. C.
Subjects: 3' Untranslated regions ; Alleles ; Asian Continental Ancestry Group ; Asians ; Autoimmune diseases ; Biological Sciences ; Data processing ; Gender differences ; Gene polymorphism ; Genes ; Genetic Diseases, X-Linked - genetics ; Genetic loci ; Genetic Predisposition to Disease ; Genotypes ; Heterozygotes ; Human genetics ; Humans ; Interferon ; Lupus ; Lupus Erythematosus, Systemic - genetics ; Male ; Males ; Messenger RNA ; Polymorphism ; Polymorphism, Single Nucleotide ; Rheumatology ; RNA, Messenger - genetics ; Sex chromosomes ; Sex differences ; Sex Factors ; Single-nucleotide polymorphism ; Systemic lupus erythematosus ; TLR7 protein ; Toll-Like Receptor 7 - genetics ; Toll-like receptors ; X chromosome
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2010-09, Vol.107 (36), p.15838-15843
Description: 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 × 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 × 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.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.1001337107
PMID: 20733074
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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

Copyright © 1993-2008 The National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Sep 7, 2010 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1001337107 ;PMID: 20733074

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