Objective: Acute necrotizing encephalopathy (ANE) is a severe complication of infectious diseases affecting the brain and systemic organs. The main pathogenesis is cytokine storm, in which interleukin-6 (IL-6) and interleukin-10 (IL-10) are candidates for key cytokines. To further elucidate their roles in the etiology and pathogenesis of ANE, we studied polymorphisms in the promotor regions of the and genes by genetic and functional analyses.
Methods: We first conducted a case-control association study of four and three polymorphisms. We genotyped 31 Japanese ANE cases and compared the results with those of approximately 200 Japanese controls. For the two polymorphisms showing a possible association, we next studied whether the polymorphisms alter the production of IL-6 or IL-10 by lymphoblasts upon phorbol 12-myristate 13-acetate (PMA) stimulation.
Results: The frequencies of rs1800796G allele and rs1800871/rs1800872 CC/CC diplotype were significantly higher in ANE cases than in controls. The CC/CC diplotype was associated with low IL-10 production, whereas the GG genotype was not associated with IL-6 production.
Conclusion: rs1800871/rs1800872 CC/CC diplotype may predispose Japanese children to ANE by altering IL-10 production in the early phase of infection. Etio-pathogenetic significance of rs1800796G remains to be elucidated.
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| http://dx.doi.org/10.3389/fnins.2023.1231957 | DOI Listing |
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