Moreover, both studies, Jang et al. [24] and our, showed that the total frequency of the AA haplotype was highest (90.3% and 85.3%, respectively) and the GG haplotype was lowest (4.5% and 0.6%, respectively) in diseased patients and controls. Some authors have reported that gender differences in the disease phenotype among patients
with RA; however, no statistically Neratinib mw gender differences were noted at diagnosis (Table 1). Our findings have shown that both analysed IL-17F gene polymorphisms were not associated with gender. We also have shown that the impact of the His161Arg IL-17F gene polymorphism was more significant than that of the Glu126Gly. Our detailed genotype–phenotype analysis indicated that IL-17F 161Arg variant was Vemurafenib chemical structure associated with higher number of tender joints (P = 0.03), higher mean value of DAS-28-CRP and higher HAQ score, suggesting that this polymorphism might be associated with an increased disease activity (Table 4). Moreover, our findings have shown that patients with RA with rare allele of the IL-17F Glu126Gly variant had a tendency to have longer
disease duration than a carrier of two wild-type alleles (P = 0.07, Table 5). Perhaps the IL-17F His161Arg and/or Glu126Gly substitution may directly regulate the IL-17F expression. IL-17A, IL-17F and IL-23 may play an important role in T-cell-triggered inflammation by upregulating some of gene products involved in cell activation, proliferation and growth and it is an important inductor of various cytokines and chemokines that are crucial in regulating inflammatory response [37]. Our hypothesis suggests
that polymorphisms in the IL-17 gene may cause redundant production of some proinflammatory Selleck Gefitinib cytokines, such as IL-1β and TNF-α, which can mediate inflammatory pathology in many autoimmune diseases, including RA. In addition, in autoimmune diseases, TNF-α is responsible for the inflammatory and protective aspects, and IL-1β is responsible for the destructive processes [37]. Moreover, IL-1β polymorphism was also associated with the parameters of disease activity [data not shown]. And maybe the relationship between IL-17F and severity of RA is connected with expression of IL-1β or other proinflammatory cytokines. Only two other genetic studies have shown relationship between IL-17 family cytokine and RA, however, they analysed IL-17A but not IL-17F [38, 39]. Nordang GB et al. [39] analysed the IL-17 gene by tagging the main genetic variation and they found a weak but significant correlation with the IL-17A promoter polymorphism, rs2275913, in Norwegian patients with RA. However, Furuya et al. [38] examined the association between SE, age at RA onset, radiographic progression in Japanese patients with early RA and three SNPs in the IL-17A gene, rs3804513, rs3748067, rs1974226. They suggested that rs3804513 IL-17A gene polymorphism may be associated with radiographic progression in patients with RA.