The ability of IL-17 to induce nitric oxide synthesis in cartilage,

production of proinflammatory cytokines in selleck peripheral blood macrophages and collagenases in chondrocytes implies its role in cartilage biology [30, 31]. Here we investigated for the first time the role of the IL-17F gene polymorphisms on susceptibility and severity of RA in Polish population. We analysed two polymorphisms in the IL-17F gene at positions 7383 A/G and 7488 A/G. Both SNPs are localized in exon 3, which caused the substitution of adenine to guanine, and they also change amino acid in the protein sequence. The first SNP at position 7383A/G changes glutamic acid (GAG) to glycine (GGG), the second SNP at position 7844A/G changes histidine (CAT) to arginine (CGT). The results of this study showed that are no significant differences between patients with RA and control subjects in genotypes distribution and alleles frequencies for the polymorphisms click here Glu126Gly and His161Arg of the IL-17F gene (Table 2). The allele frequencies of IL-17F polymorphisms were studied with HapMap project. They showed some differences in comparison with other populations. The minor allele frequency of His161Arg

variants was lower for the Polish subjects (3.8%) than for the populations from Canada, United States of America, United Kingdom, China, Japan and Nigeria, but the minor allele frequency of Glu126Gly polymorphism was higher in our group (10%) compared with the other populations. Moreover, in populations from Nigeria and Japan was detected only wild-type allele for Glu126Gly. There are few reports that showed the correlation of the IL-17F His161Arg

and Glu126Gly polymorphisms with development and course of human disorders. Southam L et al. [30] studied the association of both polymorphisms with susceptibility to the osteoarthritis. Methamphetamine However, they did not find differences in His161Arg and Glu126Gly IL-17F genotypes distribution and alleles frequencies between patients with osteoarthritis and healthy groups. Kawaguchi M et al. [25] reported that rare allele G of the IL-17F His162Arg polymorphism is inversely associated with development of asthma, and low frequency of polymorphic homozygote suggests that the His162Arg variant does not contribute substantially to the disease at the population. They also showed that functional consequences of this polymorphism, which was examined by using recombinant wild-type and mutant IL-17F proteins, may be suppressed expression and activity of IL-17F in carriers of rare allele G. These authors also demonstrated that the IL-17F coding variant of His161Arg, which is associated with impaired IL-17F signalling, blocked induction of IL-8 expression by wild-type IL-17F in vitro functional experiments. In a recent study, Ramsey et al. [32], using Caucasian female, found no correlation between IL-17F polymorphisms (including His161Arg) and asthma.