Interleukin 17A gene polymorphism in patients with rheumatoid arthritis

Interleukin 17 plays a key role in the immunopathogenesis of rheumatoid arthritis (RA) and serves as a link between activation of innate and adaptive immune cells, whereas its increased expression may represent one of the causes for uncontrolled inflammation and formation of immunopathological reactions. Among members of the interleukin 17 family, most studied is IL-17A, which is characterized by peak biological activity. IL-17A is one of the important immune mediators able to induce production of other pro-inflammatory cytokines and chemokines and promote recruitment of inflammatory cells, such as monocytes and neutrophils, into inflamed organs. IL17A gene contains a number of polymorphic sites, wherein single-nucleotide substitutions particularly at position the -197G/A may affect its expression level. Here in case-control study we retrospectively examined contribution of genetic polymorphism at the -197G/A position within the IL17A gene. Allele-specific PCR was used to iderntify the -197G/A polymorphism in IL17A gene in groups of patients with rheumatoid arthritis and healthy donors of the Russian ethnic group. Our study was made within a framework on assessing immunogenetic component for rheumatoid arthritis in ethnic Russian subjects in the Chelyabinsk Region. Prevalence of IL17A gene alleles and genotypes obtained in the work is in agreement with the Hardy– Weinberg equilibrium, and is characterized by rather high frequency of allele replacement (40%), which is typical for Caucasoid populations. Thus, it was found that interpopulation differences are characteristic of such gene polymorphism shown not to be associated with predisposition to rheumatoid arthritis in ethnic Russian subjects in the Chelyabinsk Region. Women with RA in our study were found to display certain changfes in frequencies of alleles and genotypes formed due to single-nucleotide substitution in IL17A gene at position -197G/A. However, in women such features cannot be considered as additional risk factors for developing RA. Allele -197*G, homozygous genotype -197G/G may be considered as markers of late-onset for the first RA attack in women. Analysis on distribution of SNP -197G/A alleles and genotypes within the IL17A gene showed that such polymorphism is of low value predictor likely being more associated with some RA clinical variants, but not with predisposition to RA development.