ABSTRACT
OBJECTIVE: Previous studies implicated that IL17/IL23 pathway and TH17 cells play an important role in autoimmune inflammation. Genome wide association studies have identified multiple single nucleotide polymorphisms (SNPs) in the IL23R and IL17 genes region associated with rheumatoid arthritis (RA). METHODS: In this study, we investigated the association of IL23R, IL17A and IL17F genes SNPs with RA susceptibility in the Algerian population. 343 patients with RA and 323 healthy subjects were genotyped for IL23R (rs11209026, rs1343151, rs10489629), IL17F (rs763780, rs2397084) and IL17A (rs2275913) variants by TaqMan technology. RESULTS: There was no evidence of a genetic association between IL23R, IL17F and IL17A SNPs and RA susceptibility in our population. However, IL23R rs1343151 variant enhanced the development of RF IgM and IgG positive (+) RA as compared with RF IgM and IgG negative (-) RA (OR 2.29, p = 0.004 and OR 0.64, p = 0.014 respectively). Also, IL23R rs10489629 was associated with all RF isotypes positive disease (IgM+: OR 2.16, p = 0,006; IgG+: OR 0.64, p = 0,004 and IgA+: OR 1.54, p = 0,013). A moderate association of IL17A rs2275913 with RF IgA- RA subgroup was shown (OR 1.95, p = 0,039). Moreover, our data showed a correlation between IL23R and IL17F variants and the parameters of disease activity such as HAQ score and disease duration. CONCLUSION: The current study emphasizes the lack of association of IL23R and IL17 polymorphisms with RA susceptibility in the Algerian population. However, the data showed the relationship between IL23R and IL17A polymorphisms and the production of the different RF isotypes in RA patients.
Subject(s)
Arthritis, Rheumatoid/genetics , Genome-Wide Association Study , Interleukin-17/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin/genetics , Adult , Algeria , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
Increasing evidence suggests that the rs6822844, within KIAA1109/TENR/IL2/IL21 gene cluster on 4q27, is strongly associated with rheumatoid arthritis (RA) in the Caucasian population. The aim of this study is to investigate the possible association between the SNP rs6822844 and susceptibility to RA in the Algerian Maghreb population, and to explore the association with the clinical and immunological features of RA. The polymorphism rs6822844 was genotyped in 323 RA patients and 323 healthy individuals using the TaqMan assay. A strong association of IL2/IL21 with RA susceptibility was detected in the Algerian population [odds ratio (OR) = 2.57 (95% confidence interval (CI) 1.74-3.83), P = 10(-4) ]. Our results revealed that IL2/IL21 predisposed to disease development in both autoantibody positive and negative disease. Meanwhile, the association was stronger in RA patients with anti-cyclic citrullinated peptides (ACPA) positive than those with ACPA negative [OR = 2.30 (95% CI 1.53-3.51), P = 10(-4) and OR = 1.98 (95% CI 1.01-4.22), P = 0.037, respectively]. Moreover, our findings showed a moderate association of the rs6822844 polymorphism with disease activity (P = 0.014). This study indicates for the first time that there is a strong association between IL2/IL21 rs6822844 variant and susceptibility to RA in the Algerian population, and that this association was independent from the autoantibodies status of RA patients.
