Sex-specific Association of X-linked Toll-like Receptor 7 (TLR7) with Male Systemic Lupus Erythematosus

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Aug 25

PMID 20733074

Citations 164

Authors

Nan Shen

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

Affiliations

Soon will be listed here.

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.

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