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Cited by 262

The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.

A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus

Open access
Luo, Xiaobing, Yang, Wanling, Ye, Dong-Qing, Cui, Huijuan, Zhang, Yan, Hirankarn, Nattiya, Qian, Xiaoxia, Tang, Yuanjia, Lau, Yu Lung, de Vries, Niek, Tak, Paul Peter, Tsao, Betty P., Shen, Nan·2011·PLoS Genetics
DOI 10.1371/journal.pgen.1002128
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Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329) in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (P(meta) = 2.74×10(-8), odds ratio = 1.29 [1.18-1.40]). The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients.

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Metadata

Authors
Luo, X., Yang, W., Ye, D.-Q., Cui, H., Zhang, Y., Hirankarn, N., Qian, X., Tang, Y., Lau, Y. L., de Vries, N., Tak, P. P., Tsao, B. P., & Shen, N.
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2011-06-30
Volume
7
Issue
6
Pages
e1002128
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1002128
OpenAlex
W2070017388
Cited by
262
References
45
FWCI
19.78
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus. https://app.cochat.ai/papers/10.1371/journal.pgen.1002128
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Luo, X., Yang, W., Ye, D.-Q., Cui, H., Zhang, Y., Hirankarn, N., Qian, X., Tang, Y., Lau, Y. L., de Vries, N., Tak, P. P., Tsao, B. P., & Shen, N. (2011). A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1002128

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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