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

Abstract

Abstract Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine. Disease activity and mucosal injury are affected by the Th17 cells and their interleukin (IL)-17A. A link between genetic variations in IL17A genes and autoimmunity susceptibility has been reported; however, the results in UC are limited and contradictory. The aim of this study was to evaluate the involvement of IL17A and IL17A receptor (IL17RA) variants on susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The case-control study included 104 UC patients and 213 healthy controls. Patients were divided according to the endoscopic activity: remission/mild (Mayo ≤ 1) and moderate/severe (Mayo > 1). The IL17A (rs3819024, rs3819025) and IL17RA (rs2241043, rs2241049, rs6518661) variants were genotyped by allelic discrimination using the real time polymerase chain reaction. IL-17A plasma levels were determined using microspheres immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. However, IL17A GA genotype (rs3819024) was associated to elevated levels of IL-17 only in UC patients; moreover, patients with the G allele (dominant model) of IL17RA (rs2241049) showed 2.944 more chance of developing moderate/severe disease. In conclusion, IL17A GA genotype (rs3819024) was associated with elevated IL-17A plasma levels in UC patients but not in controls. In addition, AG + GG genotypes of IL17RA (rs2241049) variant were associated to moderate/severe UC. The results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, epigenetic or environmental variables in the IL-17A expression that is present in patients with UC and absent in controls.