biostudies-literatureUnknown17Hoshino A<h4>Objective</h4>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 <i>IL6</i> and <i>IL10</i> genes by genetic and functional analyses.<h4>Methods</h4>We first conducted a case-control association study of four <i>IL6</i> and three <i>IL10</i> 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.<h4>Results</h4>The frequencies of <i>IL6</i> rs1800796G allele and <i>IL10</i> rs1800871/rs1800872 CC/CC diplotype were significantly higher in ANE cases than in controls. The <i>IL10</i> CC/CC diplotype was associated with low IL-10 production, whereas the <i>IL6</i> GG genotype was not associated with IL-6 production.<h4>Conclusion</h4><i>IL10</i> 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 <i>IL6</i> rs1800796G remains to be elucidated.Frontiers in neuroscience1231957https://www.ebi.ac.uk/biostudies/studies/S-EPMC10435083biostudies-literatureAssociation of <i>IL6</i> and <i>IL10</i> gene promotor polymorphisms with susceptibility to acute necrotizing encephalopathy.PMC10435083Mizuguchi MTakahashi NOka AHoshino AfalseAssociation of <i>IL6</i> and <i>IL10</i> gene promotor polymorphisms with susceptibility to acute necrotizing encephalopathy.<h4>Objective</h4>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 <i>IL6</i> and <i>IL10</i> genes by genetic and functional analyses.<h4>Methods</h4>We first conducted a case-control association study of four <i>IL6</i> and three <i>IL10</i> 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.<h4>Results</h4>The frequencies of <i>IL6</i> rs1800796G allele and <i>IL10</i> rs1800871/rs1800872 CC/CC diplotype were significantly higher in ANE cases than in controls. The <i>IL10</i> CC/CC diplotype was associated with low IL-10 production, whereas the <i>IL6</i> GG genotype was not associated with IL-6 production.<h4>Conclusion</h4><i>IL10</i> 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 <i>IL6</i> rs1800796G remains to be elucidated.2023-01-01T00:00:00Z20232025-04-04T08:54:10.709Z2025-04-04T08:54:10.709ZS-EPMC104350833760000010.3389/fnins.2023.1231957