Dataset Information

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 (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.

SUBMITTER: Shen N

PROVIDER: S-EPMC2936646 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Shen Nan N Fu Qiong Q Deng Yun Y Qian Xiaoxia X Zhao Jian J Kaufman Kenneth M KM Wu Yee Ling YL Yu C Yung CY Tang Yuanjia Y Chen Ji-Yih JY Yang Wanling W Wong Maida M Kawasaki Aya A Tsuchiya Naoyuki N Sumida Takayuki T Kawaguchi Yasushi Y Howe Hwee Siew HS Mok Mo Yin MY Bang So-Young SY Liu Fei-Lan FL Chang Deh-Ming DM Takasaki Yoshinari Y Hashimoto Hiroshi H Harley John B JB Guthridge Joel M JM Grossman Jennifer M JM Cantor Rita M RM Song Yeong Wook YW Bae Sang-Cheol SC Chen Shunle S Hahn Bevra H BH Lau Yu Lung YL Tsao Betty P BP

Proceedings of the National Academy of Sciences of the United States of America 20100823 36

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, ...[more]

PMID: 20733074

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Project description:OBJECTIVE:Phenome-wide association studies (PheWAS) scan across billing codes in the electronic health record (EHR) and re-purpose clinical EHR data for research. In this study, we examined whether PheWAS could function as an EHR-based discovery tool for systemic lupus erythematosus (SLE) and identified novel clinical associations in male versus female patients with SLE. METHODS:We used a de-identified version of the Vanderbilt University Medical Center EHR, which includes more than 2.8 million subjects. We performed EHR-based PheWAS to compare SLE patients with age-, sex-, and race-matched control subjects and to compare male SLE patients with female SLE patients, controlling for multiple testing using a false discovery rate (FDR) P value of 0.05. RESULTS:We identified 1,097 patients with SLE and 5,735 matched control subjects. In a comparison of patients with SLE and matched controls, SLE patients were shown to be more likely to have International Classification of Diseases, Ninth Revision codes related to the SLE disease criteria. In the PheWAS of male versus female SLE patients, with adjustment for age and race, male patients were shown to be more likely to have atrial fibrillation (odds ratio 4.50, false discovery rate P = 3.23 × 10-3 ). Chart review confirmed atrial fibrillation, with the majority of patients developing atrial fibrillation after the SLE diagnosis and having multiple risk factors for atrial fibrillation. After adjustment for age, sex, race, and coronary artery disease, SLE disease status was shown to be significantly associated with atrial fibrillation (P = 0.002). CONCLUSION:Using PheWAS to compare male and female patients with SLE, we identified a novel association of an increased incidence of atrial fibrillation in male patients. SLE disease status was shown to be independently associated with atrial fibrillation, even after adjustment for age, sex, race, and coronary artery disease. These results demonstrate the utility of PheWAS as an EHR-based discovery tool for SLE.

Dataset Information

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

Publications

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

Similar Datasets

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