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11.12.2017 | Original Research Paper

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients

verfasst von: Catarina Addobbati, Heidi Lacerda Alves da Cruz, José Eduardo Adelino, Amanda Luíze Melo Tavares Ramos, Thiago Sotero Fragoso, Alexandre Domingues, Ângela Luiza Branco Pinto Duarte, Renê Donizeti Ribeiro Oliveira, Paulo Louzada-Júnior, Eduardo Antônio Donadi, Alessandra Pontillo, Jaqueline de Azevêdo Silva, Sergio Crovella, Paula Sandrin-Garcia

Erschienen in: Inflammation Research | Ausgabe 3/2018

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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.

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Titel: Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients
verfasst von: Catarina Addobbati
Heidi Lacerda Alves da Cruz
José Eduardo Adelino
Amanda Luíze Melo Tavares Ramos
Thiago Sotero Fragoso
Alexandre Domingues
Ângela Luiza Branco Pinto Duarte
Renê Donizeti Ribeiro Oliveira
Paulo Louzada-Júnior
Eduardo Antônio Donadi
Alessandra Pontillo
Jaqueline de Azevêdo Silva
Sergio Crovella
Paula Sandrin-Garcia
Publikationsdatum: 11.12.2017
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 3/2018
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-017-1119-2

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Abstract

Objective

Materials and methods

Results

Conclusions

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