Polymorphisms in inflammasome genes and risk of asthma in Brazilian children

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dc.citation.volume93
dc.contributor.authorCordeiro Leal, Vinicius Nunes
dc.contributor.authorGenov, Isabel Rugue [UNIFESP]
dc.contributor.authorMallozi, Marcia C. [UNIFESP]
dc.contributor.authorSole, Dirceu [UNIFESP]
dc.contributor.authorPontillo, Alessandra
dc.coverageOxford
dc.date.accessioned2020-07-02T18:52:06Z
dc.date.available2020-07-02T18:52:06Z
dc.date.issued2018
dc.description.abstractConsidering its role in inflammation and recently described "alternative" roles in epithelial homeostasis and Th1/Th2 balance, we hypothesize that inflammasome genetics could contribute to the development of asthma. Selected functional polymorphisms in inflammasome genes are evaluated in a cohort of asthmatic children and their families. Gain-of-function NLRP1 variants rs11651270, rs12150220 and rs2670660 resulted significantly associated to asthma in trios (TDT) analysis; and rs11651270 and rs2670660 also with asthma severity and total IgE level in asthmatic children. NLRP1 activators in humans are still unknown, however we hypothesized that individuals with gain-of-function SNPs in NLRP1 could be more prone in activating inflammasome in the presence of asthma-related cell stressors (i.e. ER stress or ROS), and this activation contribute to exacerbate inflammatory response and asthma development. Gain-of-function IL1A rs17561 resulted significantly associated with a reduced pulmonary capacity in asthmatic children. IL18 rs5744256 which lead to lower serum level of IL-18 appeared to be associated to a worse response to bronchodilators. Concluding, this work provides evidences about the contribution of inflammasome genetics in the development of paediatric asthma, both considering its inflammatory role in alveolar macrophages (i.e.: NLRP1) or its homeostatic role in lung epithelial cells (i.e.: IL1A, IL18).en
dc.description.affiliationUniv Sao Paulo, ICB, Dept Imunol, Lab Imunogenet, Ave Prof Lineu Prestes 1730,Cidade Univ, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pediat, Ambulatorio Alergia Imunol Clin & Reumatol, UNIFESP, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Pediat, Ambulatorio Alergia Imunol Clin & Reumatol, UNIFESP, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research foundation (FAPESP)
dc.description.sponsorshipCNPq
dc.description.sponsorshipFAPESP
dc.description.sponsorshipIDFAPESP: 2015/23345-6
dc.format.extent64-67
dc.identifierhttp://dx.doi.org/10.1016/j.molimm.2017.11.006
dc.identifier.citationMolecular Immunology. Oxford, v. 93, p. 64-67, 2018.
dc.identifier.doi10.1016/j.molimm.2017.11.006
dc.identifier.fileWOS000424181000008.pdf
dc.identifier.issn0161-5890
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53881
dc.identifier.wosWOS:000424181000008
dc.language.isoeng
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofMolecular Immunology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAsthmaen
dc.subjectInflammasomeen
dc.subjectNLRP1en
dc.subjectIL1Aen
dc.subjectIL18en
dc.titlePolymorphisms in inflammasome genes and risk of asthma in Brazilian childrenen
dc.typeinfo:eu-repo/semantics/article
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