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
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