Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a progressive, autoimmune disease for which the previous studies have shown that some functional polymorphisms can influence its etiology. Knowing this, the aim of this study was to investigate the association of +2199 A/C IL-23R (rs10889677), -197 G/A IL-17A (rs2275913), and +7488 A/G IL-17F (rs763780) gene polymorphisms with RA susceptibility and clinical features in a Brazilian population. A total of 127 RA patients and 134 healthy controls were recruited for the analyses of polymorphic variants. Genotyping was performed using RFLP-PCR. Logistic regression was used to analyze the genotype distribution of the polymorphisms. Individuals carrying the homozygous CC genotype for the IL-23R polymorphism seem to be at lower risk for RA development (OR 0.22; p = 0.004), as well as those carrying the variant C allele (OR 0.56; p = 0.002). For the -197 G/A IL-17A polymorphism, the wild-type genotype (GG) was significantly associated with a 3.18-fold (OR 3.18; p = 0.033) increased risk for RA. In relation to the +7488 A/G IL-17F polymorphism, no significant difference was found between RA cases and control subjects (p > 0.05). Moreover, when investigating the relationship between polymorphisms and clinical features, no evidence of an association was found. Our findings suggest that the variants +2199 A/C IL-23R and -197 G/A IL-17A could contribute to RA development in the studied population. However, larger studies are needed to fully understand this genetic predisposition.

IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis

“…Again, most of published studies performed in Algerian [ 27 ], Polish [ 28 , 29 ], Brazilian [ 30 ] and Chinese [ 31 ] populations emphasized the lack of association between the IL-17A rs2275913 and RA risk. Nevertheless, two studies performed in Norwegian [ 32 ] and Brazilian [ 33 ] reported that the rs2275913 polymorphism increased risk of RA. In Norwegian patients, the IL-17A*G allele conferred a weak risk, OR = 1.17, 95% CI = 1.02–1.34 [ 32 ].…”

“…In Norwegian patients, the IL-17A*G allele conferred a weak risk, OR = 1.17, 95% CI = 1.02–1.34 [ 32 ]. While the risk for RA was moderate for the IL-17*G/G genotype, OR = 3.18, 95% CI = 1.13–9.95 in the Brazilian study [ 33 ]. Accordingly, the meta-analysis of Lee et al [ 17 ] the IL-17A*A allele conferred a weak protective role for RA risk, OR = 0.866; 95% CI = 0.794–0.944.…”

Influence of TNF and IL17 Gene Polymorphisms on the Spondyloarthritis Immunopathogenesis, Regardless of HLA-B27, in a Brazilian Population

“…Our group already reported that the AA genotype and A allele for IL17A were associated with susceptibility to chronic periodontitis in South Brazil, highlighting their involvement in a chronic inflammatory condition [ 18 ]. A weak association between rheumatoid arthritis and the promoter IL17A rs2275913 was found in the Norwegian population and more recently in the Brazilian population [ 7 , 32 ]. Specifically, with the risk of AS and its severity, a strong association was observed with the rs4819554 SNP in the promoter region of IL17RA in two Spanish cohorts of patients and controls, but not involving the IL17A and IL17F polymorphisms that we have studied here [ 33 ].…”

The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling

“…In PsA, treatment with anti‐IL‐23 antibodies have shown beneficial effects but not in RA so far. Another finding supporting this hypothesis, is the notion that polymorphisms in the IL‐23 receptor (IL‐23R) have been linked to susceptibility for psoriasis and PsA , but are still a matter of debate in RA (Table ) .…”