Our results showed that rs10754558 NLRP3 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.
(ii) The CARD8p.C10X polymorphism in allelic model (OR = 0.995,), genotypic models (OR1 = 0.997; OR2 = 1.052; OR3 = 0.950), dominant (OR = 1.033) and recessive models (OR = 0.963) were not associated with the risk of RA (all P > 0.05).
NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for traditional risk factors, antirheumatic treatment, and age at the onset of RA.
This study found evidence of modulation of the NLRP3-inflammasome in patients with RA prior to receiving infliximab and some evidence of association for SNPs at NLRP3 and CARD8 loci with RA susceptibility and response to anti-TNF.
No statistically significant differences in allele or genotype frequencies for the rs2043211CARD8 gene variant between patients with RA and controls were seen.
This study suggests that variations in the innate immunity genes CARD8 (p.C10X) and NLRP3 (p.Q705K) have no effect on RA susceptibility either in the Tunisian or in the French population.
Deficiency of the NF-kappaB inhibitor caspase activating and recruitment domain 8 in patients with rheumatoid arthritis is associated with disease severity.
Overall, our findings provide molecular insight into the expression of CARD8 by NF-kappaB, and suggest that a deleterious polymorphism of CARD8 may help predict the severity of RA.