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

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

doi:10.1073/pnas.1001337107

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

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^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

282 Citations (Scopus)

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 × 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.

Original language	English
Pages (from-to)	15838-15843
Journal	PNAS: Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	36
Online published	23 Aug 2010
DOIs	https://doi.org/10.1073/pnas.1001337107
Publication status	Published - 7 Sept 2010
Externally published	Yes

Research Keywords

Autoimmunity
Disease susceptibility
Functional polymorphism
Interferon
Type I

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10.1073/pnas.1001337107

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Shen, N., Fu, Q., Deng, Y., Qian, X., Zhao, J., Kaufman, K. M., Wu, Y. L., Yu, C. Y., Tang, Y., Chen, J.-Y., Yang, W., Wong, M., Kawasaki, A., Tsuchiya, N., Sumida, T., Kawaguchi, Y., Howe, H. S., Mok, M. Y., Bang, S.-Y., ... Tsao, B. P. (2010). Sex-specific association of X-linked toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. PNAS: Proceedings of the National Academy of Sciences of the United States of America, 107(36), 15838-15843. https://doi.org/10.1073/pnas.1001337107

@article{95380e7fec1d45528b1831d5640ac03f,

title = "Sex-specific association of X-linked toll-like receptor 7 (TLR7) with male systemic lupus erythematosus",

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 (Pcombined = 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.",

keywords = "Autoimmunity, Disease susceptibility, Functional polymorphism, Interferon, Type I",

author = "Nan Shen and Qiong Fu and Yun Deng and Xiaoxia Qian and Jian Zhao and Kaufman, \{Kenneth M.\} and Wu, \{Yee Ling\} and Yu, \{C. Yung\} and Yuanjia Tang and Ji-Yih Chen and Wanling Yang and Maida Wong and Aya Kawasaki and Naoyuki Tsuchiya and Takayuki Sumida and Yasushi Kawaguchi and Howe, \{Hwee Siew\} and Mok, \{Mo Yin\} and So-Young Bang and Fei-Lan Liu and Deh-Ming Chang and Yoshinari Takasaki and Hiroshi Hashimoto and Harley, \{John B.\} and Guthridge, \{Joel M.\} and Grossman, \{Jennifer M.\} and Cantor, \{Rita M.\} and Song, \{Yeong Wook\} and Sang-Cheol Bae and Shunle Chen and Hahn, \{Bevra H.\} and Lau, \{Yu Lung\} and Tsao, \{Betty P.\}",

year = "2010",

month = sep,

day = "7",

doi = "10.1073/pnas.1001337107",

language = "English",

volume = "107",

pages = "15838--15843",

journal = "PNAS: Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "36",

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Shen, N, Fu, Q, Deng, Y, Qian, X, Zhao, J, Kaufman, KM, Wu, YL, Yu, CY, Tang, Y, Chen, J-Y, Yang, W, Wong, M, Kawasaki, A, Tsuchiya, N, Sumida, T, Kawaguchi, Y, Howe, HS, Mok, MY, Bang, S-Y, Liu, F-L, Chang, D-M, Takasaki, Y, Hashimoto, H, Harley, JB, Guthridge, JM, Grossman, JM, Cantor, RM, Song, YW, Bae, S-C, Chen, S, Hahn, BH, Lau, YL & Tsao, BP 2010, 'Sex-specific association of X-linked toll-like receptor 7 (TLR7) with male systemic lupus erythematosus', PNAS: Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 36, pp. 15838-15843. https://doi.org/10.1073/pnas.1001337107

Sex-specific association of X-linked toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. / Shen, Nan; Fu, Qiong; Deng, Yun et al.
In: PNAS: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 36, 07.09.2010, p. 15838-15843.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Sex-specific association of X-linked toll-like receptor 7 (TLR7) with male systemic lupus erythematosus

AU - Shen, Nan

AU - Fu, Qiong

AU - Deng, Yun

AU - Qian, Xiaoxia

AU - Zhao, Jian

AU - Kaufman, Kenneth M.

AU - Wu, Yee Ling

AU - Yu, C. Yung

AU - Tang, Yuanjia

AU - Chen, Ji-Yih

AU - Yang, Wanling

AU - Wong, Maida

AU - Kawasaki, Aya

AU - Tsuchiya, Naoyuki

AU - Sumida, Takayuki

AU - Kawaguchi, Yasushi

AU - Howe, Hwee Siew

AU - Mok, Mo Yin

AU - Bang, So-Young

AU - Liu, Fei-Lan

AU - Chang, Deh-Ming

AU - Takasaki, Yoshinari

AU - Hashimoto, Hiroshi

AU - Harley, John B.

AU - Guthridge, Joel M.

AU - Grossman, Jennifer M.

AU - Cantor, Rita M.

AU - Song, Yeong Wook

AU - Bae, Sang-Cheol

AU - Chen, Shunle

AU - Hahn, Bevra H.

AU - Lau, Yu Lung

AU - Tsao, Betty P.

PY - 2010/9/7

Y1 - 2010/9/7

N2 - 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 (Pcombined = 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.

AB - 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 (Pcombined = 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.

KW - Autoimmunity

KW - Disease susceptibility

KW - Functional polymorphism

KW - Interferon

KW - Type I

UR - https://www.scopus.com/pages/publications/77957673544

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-77957673544&origin=recordpage

U2 - 10.1073/pnas.1001337107

DO - 10.1073/pnas.1001337107

M3 - RGC 21 - Publication in refereed journal

C2 - 20733074

SN - 0027-8424

VL - 107

SP - 15838

EP - 15843

JO - PNAS: Proceedings of the National Academy of Sciences of the United States of America

JF - PNAS: Proceedings of the National Academy of Sciences of the United States of America

IS - 36

ER -

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

Abstract

Research Keywords

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