title: A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in central south Chinese population.
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.
authors.affiliation: Department of Dermatology, Xiang-Ya Hospital, Central South University, 87 XiangYa Road, Changsha, 410008 Hunan, People's Republic of China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: Wu
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Li
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Ye-Hong
authors.initials: YH
authors.lastname: Kuang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D044466:Asian People; D051926:Basigin / Q000235:genetics*; D001665:Binding Sites; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D011565:Psoriasis / Q000235:genetics*; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; C497886:BSG protein, human; C558125:MIRN492 microRNA, human; D035683:MicroRNAs; D051926:Basigin