Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients
Autor: | Renê Donizeti Ribeiro de Oliveira, Amanda Luíze Melo Tavares Ramos, Alexandre Domingues, Ângela Luiza Branco Pinto Duarte, Paula Sandrin-Garcia, Eduardo Antônio Donadi, José Eduardo Adelino, Paulo Louzada-Junior, Heidi Lacerda Alves da Cruz, Sergio Crovella, Alessandra Pontillo, Jaqueline de Azevêdo Silva, Thiago Sotero Fragoso, C. Addobbati |
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Přispěvatelé: | Addobbati, Catarina, da Cruz, Heidi Lacerda Alve, Adelino, José Eduardo, Melo Tavares Ramos, Amanda Luíze, Fragoso, Thiago Sotero, Domingues, Alexandre, Branco Pinto Duarte, Ângela Luiza, Oliveira, Renê Donizeti Ribeiro, Louzada-Júnior, Paulo, Donadi, Eduardo Antônio, Pontillo, Alessandra, de Azevêdo Silva, Jaqueline, Crovella, Sergio, Sandrin-Garcia, Paula |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Inflammasomes Interleukin-1beta Gene Expression Autoimmunity Severity of Illness Index Arthritis Rheumatoid AUTOIMUNIDADE NLRC4 Gene expression NLRP1 Caspase 1 Interleukin-18 Inflammasome Middle Aged Neoplasm Proteins DNA-Binding Proteins Female Brazil medicine.drug SNPs Adult medicine.medical_specialty Immunology Prognostic and monocytes SNP Single-nucleotide polymorphism NLR Proteins Polymorphism Single Nucleotide 03 medical and health sciences AIM2 Internal medicine NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Genetic association Adaptor Proteins Signal Transducing Aged Prognostic and monocyte Pharmacology business.industry Calcium-Binding Proteins Rheumatology CARD Signaling Adaptor Proteins 030104 developmental biology business Apoptosis Regulatory Proteins |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
Popis: | OBJECTIVE: In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)'s development and severity in the Brazilian population. MATERIALS AND METHODS: Thirteen single nucleotide polymorphisms within six inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1) as well as IL1B and IL18 genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS + ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR. RESULTS: Our results showed that rs10754558 NLRP3 and rs2043211 CARD8 polymorphisms are associated with RA development (p value = 0.044, OR = 1.77, statistical power = 0.999) and severity measured by Health Assessment Questionnaire (HAQ) (p value = 0.03), respectively. Gene expression analyses showed that RA patients display activation of CASP1, IL1B and IL1R genes independently of LPS + ATP activation. In LPS + ATP-treated monocytes, NLRP3 and NLRC4 expressions were also significantly higher in patients compared with controls. CONCLUSIONS: The first reported results in Brazilian populations support the role of inflammasome in the development of RA. |
Databáze: | OpenAIRE |
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