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.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors would like to thank the patients, their parents and all the staff in the hospitals involved in this study.
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This work has been supported by Croatian Science Foundation under the project IP-2019-04-8822.
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MBV, MH, JW, NA, MS, MS, NK, DG, KCG, AG, MF and MJ. The first draft of the manuscript was written by MBV and MS, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.
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Batnozic Varga, M., Held, M., Wagner, J. et al. The Association of HMGB1 and RAGE Gene Polymorphisms with IgA Vasculitis. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10536-0
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DOI: https://doi.org/10.1007/s10528-023-10536-0