1. Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.
- Author
-
Addobbati C, da Cruz HLA, Adelino JE, Melo Tavares Ramos AL, Fragoso TS, Domingues A, Branco Pinto Duarte ÂL, Oliveira RDR, Louzada-Júnior P, Donadi EA, Pontillo A, de Azevêdo Silva J, Crovella S, and Sandrin-Garcia P
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adult, Aged, Apoptosis Regulatory Proteins genetics, Brazil, Calcium-Binding Proteins genetics, Caspase 1 genetics, DNA-Binding Proteins genetics, Female, Gene Expression, Humans, Interleukin-18 genetics, Interleukin-1beta genetics, Male, Middle Aged, NLR Proteins, Polymorphism, Single Nucleotide, Severity of Illness Index, Arthritis, Rheumatoid genetics, CARD Signaling Adaptor Proteins genetics, Inflammasomes genetics, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Neoplasm Proteins genetics
- Abstract
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.
- Published
- 2018
- Full Text
- View/download PDF