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HMGB1 和 RAGE 基因多态性与 IgA 血管炎的关联。

The Association of HMGB1 and RAGE Gene Polymorphisms with IgA Vasculitis.

机构信息

Department of Paediatrics, Josip Juraj Strossmayer University of Osijek, Faculty of Medicine Osijek, University Hospital Centre Osijek, Osijek, Croatia.

Division of Clinical Immunology, Rheumatology and Allergology, Department of Paediatrics, University of Zagreb School of Medicine, Centre of Reference for Paediatric and Adolescent Rheumatology of Ministry of Health of the Republic Croatia, University Hospital Centre Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia.

出版信息

Biochem Genet. 2024 Jun;62(3):2268-2278. doi: 10.1007/s10528-023-10536-0. Epub 2023 Oct 30.

Abstract

High-mobility group box 1 (HMGB1) is a pleiotropic cytokine that propagates inflammation by its extracellular action of interacting with the receptor for advanced glycation end products (RAGE). Both HMGB1 and RAGE play multiple roles in the pathogenesis of a variety of inflammatory and autoimmune diseases. We investigated the association of five single-nucleotide polymorphisms (SNPs) of the HMGB1 gene (rs1412125, rs2249825, rs1045411, rs1060348, rs41369348) and four SNPs of the RAGE gene (rs1800624, rs1800625, rs2070600, rs3134940) with the susceptibility and clinical features of paediatric patients with IgA vasculitis (IgAV), also known as Henoch-Schönlein's purpura. This case‒control study included 103 children with IgAV (experimental group) and 150 age-matched healthy individuals (control group). The strength of the association between different groups and alleles or genotypes of HMGB1 and RAGE was estimated using odds ratios (ORs) and 95% confidence intervals (CIs). The HMGB1 polymorphisms rs41369348, rs1045411, rs2249825 and rs1412125 were associated with the development of generalized purpuric rash, and rs1412125 was associated with IgAV nephritis (IgAVN). The RAGE polymorphism rs2070600 might be linked to the development of arthritis in IgAV patients. There was no statistically significant association between the analysed polymorphisms and susceptibility to IgAV. This is the first study to propose an association between several HMGB1 and RAGE polymorphisms and different phenotypes in the clinical course of IgAV in a paediatric population. Further research on other polymorphisms of HMGB1 and RAGE should be conducted in a larger number of patients.

摘要

高迁移率族蛋白 B1(HMGB1)是一种多效细胞因子,通过与晚期糖基化终产物受体(RAGE)的细胞外相互作用来传播炎症。HMGB1 和 RAGE 在多种炎症和自身免疫性疾病的发病机制中都发挥着多种作用。我们研究了 HMGB1 基因的 5 个单核苷酸多态性(SNP)(rs1412125、rs2249825、rs1045411、rs1060348、rs41369348)和 RAGE 基因的 4 个 SNP(rs1800624、rs1800625、rs2070600、rs3134940)与小儿 IgA 血管炎(IgAV)易感性和临床特征的关系,IgAV 也称为过敏性紫癜。这项病例对照研究纳入了 103 例 IgAV 患儿(实验组)和 150 名年龄匹配的健康个体(对照组)。使用比值比(OR)和 95%置信区间(CI)来估计不同组和 HMGB1 和 RAGE 等位基因或基因型之间的关联强度。HMGB1 多态性 rs41369348、rs1045411、rs2249825 和 rs1412125 与泛发性紫癜性皮疹的发生有关,rs1412125 与 IgAVN 有关。RAGE 多态性 rs2070600 可能与 IgAV 患者关节炎的发生有关。分析的多态性与 IgAV 的易感性之间没有统计学上的显著关联。这是第一项研究提出了几个 HMGB1 和 RAGE 多态性与儿科人群 IgAV 临床过程中不同表型之间的关联。应在更大数量的患者中对 HMGB1 和 RAGE 的其他多态性进行进一步研究。

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