A miRNA-492 binding-site polymorphism in <Emphasis Type="Italic">BSG</Emphasis> (<Emphasis Type="Italic">basigin</Emphasis>) confers risk to psoriasis in Central South Chinese population |
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Authors: | Li-Sha Wu Fang-Fang Li Liang-Dan Sun Dai Li Juan Su Ye-Hong Kuang Gang Chen Xiao-Ping Chen Xiang Chen |
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Institution: | (1) Department of Dermatology, Xiang-Ya Hospital, Central South University, 87 XiangYa Road, Changsha, 410008, Hunan, People’s Republic of China;(2) State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui, People’s Republic of China;(3) Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, 410078, Hunan, China; |
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Abstract: | 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. |
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