Polymorphisms in inflammasome genes and risk of asthma in Brazilian children

Polymorphisms in inflammasome genes and risk of asthma in Brazilian children

Author Cordeiro Leal, Vinicius Nunes Google Scholar
Genov, Isabel Rugue Autor UNIFESP Google Scholar
Mallozi, Marcia C. Autor UNIFESP Google Scholar
Sole, Dirceu Autor UNIFESP Google Scholar
Pontillo, Alessandra Google Scholar
Abstract Considering 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).
Keywords Asthma
Inflammasome
NLRP1
IL1A
IL18
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor Sao Paulo Research foundation (FAPESP) [2015/23345-6]
CNPq
FAPESP
Grant number FAPESP [2015/23345-6]
Date 2018
Published in Molecular Immunology. Oxford, v. 93, p. 64-67, 2018.
ISSN 0161-5890 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 64-67
Origin http://dx.doi.org/10.1016/j.molimm.2017.11.006
Access rights Closed access
Type Article
Web of Science ID WOS:000424181000008
URI https://repositorio.unifesp.br/handle/11600/53881

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