Involvement of IL17A and IL17RA variants in interleukin-17A levels and disease activity in ulcerative colitis

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor ( IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG +GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.