Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients
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.
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.
The first reported results in Brazilian populations support the role of inflammasome in the development of RA.
KeywordsSNPs Autoimmunity Prognostic and monocytes
This work was supported by the following Brazilian funding agencies: CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPESP (Fundação Amparo à Pesquisa do Estado de São Paulo) and FACEPE (Fundação de Amparo à Ciência e Tecnologia de Pernambuco).
CAJC conducted experiments, wrote the manuscript and prepared the tables and figures; HLAC, JEA and ALMTR helped conducting the experiments and provided insightful suggestions to the manuscript; PSG, JAS, AP and SC assisted in the study design and coordination, and read, corrected and provided major suggestions to this manuscript; TSF, AD, LFRJ, ALBPD, RDRO, PLJ and EAD recruited patients and participated in data acquisition. All authors addressed important intellectual content and approved the final manuscript for publication.
Compliance with ethical standards
Conflict of interest
The authors have declared no conflicts of interest.
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