A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in Central South Chinese population
A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in Central South Chinese population
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BSG（basigin）中的 miRNA-492 结合位点多态性增加了中国中南人群患银屑病的风险
DOI：
10.1007/s00439-011-1026-5
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发表时间：
2011-12-01
期刊：
影响因子：
5.3
通讯作者：
Chen, Xiang
中科院分区：
文献类型：
--
作者：
Wu, Li-Sha;Li, Fang-Fang;Chen, Xiang
银屑病（PS; MIM#177900）是一种慢性炎症性免疫介导的皮肤病。虽然这种疾病被认为是由遗传、免疫和环境因素共同引起的，但其完整的病因尚未完全了解。在这里，我们专注于BSG（MIM#109480），免疫球蛋白超家族的成员在循环免疫细胞群中广泛表达。我们观察到银屑病患者PBMC中BSG的表达水平升高。为了了解这种变化的潜在机制，我们对668名银屑病患者和1,143名健康对照者的BSG基因3 'UTR中的rs 8259 T>A SNP进行了基因分型。rs 8259 T等位基因与银屑病易感性显著降低相关（OR = 0.758，95%CI 0.638-0.901，p = 0.002）。有趣的是，rs 8259多态性位于miR-492结合的种子区域。通过荧光素酶报告基因测定，miR-492能够与携带rs 8259 T等位基因的BSG 3 'UTR序列结合。用A取代T消除了miR-492结合。携带rs 8259 AA基因型患者的PBMC中BSG蛋白表达显著高于携带rs 8259 TT基因型患者。我们的研究表明，miR-492可能在生理上抑制BSG表达，BSG rs 8259多态性通过影响miR-492结合而与银屑病易感性降低相关。
Psoriasis (PS; MIM#177900) is a chronic inflammatory immune-mediated skin disorder. Although the disease is believed to be caused by a combination of genetic, immunologic and environmental factors, its complete etiology has not been fully understood. Here, we focused on the BSG (MIM#109480), a member of the immunoglobulin superfamily expressed ubiquitously in circulating immune cell populations. We observed that the expression level of BSG in PBMCs was elevated in psoriasis patients. To understand the underlying mechanism for this change, we genotyped the rs8259 T>A SNP located in the 3'UTR of the BSG gene from 668 psoriasis patients and 1,143 healthy controls. The rs8259 T allele was associated with significantly decreased psoriasis susceptibility (OR = 0.758, 95% CI 0.638-0.901, p = 0.002). Interestingly, the rs8259 polymorphism was located in a seed region for miR-492 binding. The miR-492 was able to bind to the BSG 3'UTR sequence bearing the rs8259 T allele as assayed by luciferase reporter gene assay. The substitution of T with A abolished miR-492 binding. BSG protein expression in PBMCs from patients carrying the rs8259 AA genotype was significantly higher than in those from patients carrying the rs8259 TT genotype. Our study suggests that miR-492 may physiologically suppress BSG expression and the BSG rs8259 polymorphism is associated with decreased psoriasis susceptibility through affecting miR-492 binding.