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

被引：240

作者：

Shen, Nan ^{[1
,2
,3
]}

Fu, Qiong ^{[1
,2
,3
,4
]}

Deng, Yun ^{[1
,2
,3
,4
]}

Qian, Xiaoxia ^{[1
,2
,3
]}

Zhao, Jian ^{[4
]}

Kaufman, Kenneth M. ^{[5
]}

Wu, Yee Ling ^{[6
,7
]}

Yu, C. Yung ^{[6
,7
]}

Tang, Yuanjia ^{[1
,2
,3
]}

Chen, Ji-Yih ^{[8
]}

Yang, Wanling ^{[9
]}

Wong, Maida ^{[4
]}

Kawasaki, Aya ^{[10
]}

Tsuchiya, Naoyuki ^{[10
]}

Sumida, Takayuki ^{[10
]}

Kawaguchi, Yasushi ^{[11
]}

Howe, Hwee Siew ^{[12
]}

Mok, Mo Yin ^{[13
]}

Bang, So-Young ^{[14
]}

Liu, Fei-Lan ^{[15
]}

Chang, Deh-Ming ^{[16
]}

Takasaki, Yoshinari ^{[17
]}

Hashimoto, Hiroshi ^{[17
]}

Harley, John B. ^{[5
]}

Guthridge, Joel M. ^{[18
]}

Grossman, Jennifer M. ^{[4
]}

Cantor, Rita M. ^{[19
]}

Song, Yeong Wook ^{[20
]}

Bae, Sang-Cheol ^{[14
]}

Chen, Shunle ^{[1
,2
,3
]}

Hahn, Bevra H. ^{[4
]}

Lau, Yu Lung ^{[9
]}

Tsao, Betty P. ^{[4
]}

机构：

[1] Chinese Acad Sci, Joint Mol Rheumatol Lab, Inst Hlth Sci, Shanghai 200001, Peoples R China

[2] Chinese Acad Sci, Shanghai Jiao Tong Univ, Shanghai Renji Hosp, Sch Med, Shanghai 200001, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200001, Peoples R China

[4] Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90095 USA

[5] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA

[6] Nationwide Childrens Hosp, Ctr Mol & Human Genet, Res Inst, Columbus, OH 43205 USA

[7] Ohio State Univ, Columbus, OH 43205 USA

[8] Chang Gung Univ, Div Allergy Immunol & Rheumatol, Chang Gung Mem Hosp, Tao Yuan 333, Taiwan

[9] Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong 10000, Hong Kong, Peoples R China

[10] Univ Tsukuba, Ibaraki 3058577, Japan

[11] Tokyo Womens Med Univ, Inst Rheumatol, Tokyo 1628666, Japan

[12] Tan Tock Seng Hosp, Dept Rheumatol Allergy & Immunol, Singapore 308433, Singapore

[13] Univ Hong Kong, Div Rheumatol & Clin Immunol, Hong Kong 10000, Hong Kong, Peoples R China

[14] Hanyang Univ, Dept Rheumatol, Hosp Rheumat Dis, Seoul 133792, South Korea

[15] Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, Taiwan

[16] Tri Serv Gen Hosp, Natl Def Med Ctr, Taipei 114, Taiwan

[17] Juntendo Univ, Tokyo 1138421, Japan

[18] Oklahoma Med Res Fdn, Clin Immunol Program, Oklahoma City, OK 73104 USA

[19] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90024 USA

[20] Seoul Natl Univ, Div Rheumatol, Seoul 151742, South Korea

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 36期

基金：

美国国家卫生研究院; 日本学术振兴会; 中国国家自然科学基金;

关键词：

functional polymorphism; disease susceptibility; autoimmunity; type I interferon; PLASMACYTOID DENDRITIC CELLS; GENOME-WIDE ASSOCIATION; DISEASE-ACTIVITY; CHROMOSOME INACTIVATION; AUTOIMMUNE-DISEASES; COPY NUMBER; CAG REPEAT; GENE; VARIANTS; INTERFERON;

D O I：

10.1073/pnas.1001337107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：15838 / 15843

页数：6

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