Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

Autor(es)

Soares, Jaine L. S. ^[1] ; Fernandes, Fernanda Pereira ^[1] ; Patente, Thiago Andrade ^[2] ; Monteiro, Maria B. ^[3] ; Parisi, Maria C. ^[4] ; Giannella-Neto, Daniel ^[5] ; Correa-Giannella, Maria L. ^{[3, 5]} ; Pontillo, Alessandra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunogenet, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Tumores, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Lab Carboidratos & Radioimunoensaios LIM 18, Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Fac Med, Div Endocrinol, Dept Clin Med, Campinas, SP - Brazil

^[5] Univ Nove Julho UNINOVE, Programa Posgrad Med, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Immunology; v. 187, p. 46-49, FEB 2018.
• Citações Web of Science: 6

Resumo

Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p(adj) < 0.01), and rs11651270 also with a lower risk of new renal events during follow-up (p(adj) = 0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 15/23395-6 - Imunogenetica do inflamassoma, estudo translacional "da clinica a bancada,da bancada a clinica":analise das variações nos genes do inflamassoma em doenças autoinflamatorias monogênicas e multifatoriais para diagnostico diferencial e aplicações terapêutica
• Beneficiário: Alessandra Pontillo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/09276-3 - Estudo de Polimorfismos em Genes que Codificam Enzimas Antioxidantes e Transportadores de Glicose e sua Associação com a Susceptibilidade a Complicações Crônicas em Pacientes Diabéticos Tipo 1
• Beneficiário: Maria Lucia Cardillo Corrêa Giannella
• Modalidade de apoio: Auxílio à Pesquisa - Regular