Catarina Addobbati1,2, Heidi Lacerda Alves da Cruz3, José Eduardo Adelino4,3, Amanda Luíze Melo Tavares Ramos3, Thiago Sotero Fragoso5, Alexandre Domingues6, Ângela Luiza Branco Pinto Duarte6, Renê Donizeti Ribeiro Oliveira7, Paulo Louzada-Júnior7, Eduardo Antônio Donadi7, Alessandra Pontillo8, Jaqueline de Azevêdo Silva4,3, Sergio Crovella4,3, Paula Sandrin-Garcia4,3. 1. Department of Genetics, Federal University of Pernambuco, Av. Moraes Rego, 1235, Recife, Pernambuco, CEP 50760-901, Brazil. catarinaaddobbati@hotmail.com. 2. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil. catarinaaddobbati@hotmail.com. 3. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco, Recife, Pernambuco, Brazil. 4. Department of Genetics, Federal University of Pernambuco, Av. Moraes Rego, 1235, Recife, Pernambuco, CEP 50760-901, Brazil. 5. Rheumatology Service, Clinical Hospital, Federal University of Alagoas, Maceió, Alagoas, Brazil. 6. Rheumatology Division, Clinical Hospital, Federal University of Pernambuco, Recife, Pernambuco, Brazil. 7. Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. 8. Laboratory of Immunognetics, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
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.
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 RApatients 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 rs10754558NLRP3 and rs2043211CARD8 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 RApatients 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.
Entities:
Keywords:
Autoimmunity; Prognostic and monocytes; SNPs
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