Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus.
Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus.
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DOI：
10.1002/art.27223
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发表时间：
2010-02
影响因子：
--
通讯作者：
Barnes, Betsy J.
中科院分区：
文献类型：
--
作者：
Feng, Di;Stone, Rivka C.;Eloranta, Maija-Leena;Sangster-Guity, Niquiche;Nordmark, Gunnel;Sigurdsson, Snaevar;Wang, Chuan;Alm, Gunnar;Syvanen, Ann-Christine;Ronnblom, Lars;Barnes, Betsy J.
干扰素 (IFN) 调节因子 5 (IRF5) 基因的遗传变异与系统性红斑狼疮 (SLE) 易感性相关。这些变异对 SLE 患者原代血细胞中 IRF-5 表达的贡献尚未得到解决，I 型 IFN 的作用也尚未得到解决。本研究的目的是确定 SLE 患者中 IRF-5 表达增加与 IRF5 风险单倍型之间的关联。通过定量实时 PCR、小基因测定和流式细胞术测量了 44 名瑞典 SLE 患者和 16 名健康对照者的 IRF-5 转录物和蛋白质水平。对这些患者的 rs2004640、rs10954213、rs10488631 和 CGGGG 插入缺失进行了基因分型。这些多态性的基因型定义了共同的风险和保护性单倍型。与健康供体相比，SLE 患者的 IRF-5 表达和选择性剪接显着上调。转录物和蛋白质水平的增强与 IRF5 的风险单倍型相关； rs10488631 给出了唯一与非编码外显子 1C 转录增加相关的显着独立关联。小基因实验证明了 rs2004640 和 CGGGG indel 以及 I 型 IFN 在调节 IRF-5 表达中的重要作用。这项研究首次正式证明 SLE 患者原代血细胞中 IRF-5 表达和选择性剪接显着上调。风险单倍型与 SLE 患者 IRF-5 转录物和蛋白表达增强有关。
Genetic variants of the interferon (IFN) regulatory factor 5 (IRF5) gene are associated with systemic lupus erythematosus (SLE) susceptibility. The contribution of these variants to IRF-5 expression in primary blood cells of SLE patients has not been addressed, nor has the role of type I IFN. The aim of this study was to determine the association between increased IRF-5 expression and the IRF5 risk haplotype in SLE patients. IRF-5 transcript and protein levels in 44 Swedish patients with SLE and 16 healthy controls were measured by quantitative real-time PCR, minigene assay, and flow cytometry. The rs2004640, rs10954213, rs10488631 and the CGGGG indel were genotyped in these patients. Genotypes of these polymorphisms defined a common risk and protective haplotype. IRF-5 expression and alternative splicing were significantly upregulated in SLE patients versus healthy donors. Enhanced transcript and protein levels were associated with the risk haplotype of IRF5; rs10488631 gave the only significant independent association that correlated with increased transcription from non-coding exon 1C. Minigene experiments demonstrated an important role for rs2004640 and the CGGGG indel, along with type I IFNs in regulating IRF-5 expression. This study provides the first formal proof that IRF-5 expression and alternative splicing are significantly upregulated in primary blood cells of SLE patients. The risk haplotype is associated with enhanced IRF-5 transcript and protein expression in SLE patients.
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影响因子：
--
作者：
Kozyrev, Sergey V.;Lewen, Susanna;Alarcon-Riquelme, Marta E.
通讯作者：
Alarcon-Riquelme, Marta E.
DOI：
10.1101/sqb.2003.68.69
发表时间：
2003-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Fan, JB;Oliphant, A;Chee, MS
通讯作者：
Chee, MS
影响因子：
5.4
作者：
Ning, SB;Huye, LE;Pagano, JS
通讯作者：
Pagano, JS
影响因子：
4.8
作者：
Schoenemeyer, A;Barnes, BJ;Golenbock, DT
通讯作者：
Golenbock, DT
影响因子：
4.8
作者：
Hu, Guodong;Barnes, Betsy J.
通讯作者：
Barnes, Betsy J.