Il17A (rs2275913 G>A) and IL17F (rs2397084 T>C) gene polymorphisms: Relation to psoriasis risk and response to methotrexate

Background IL17F rs763780 polymorphism results in substitution of histidine to arginine at amino acid 161, leading to upregulation of IL17F and increased propensity to autoimmune diseases. The single nucleotide polymorphism rs2275913 (G197A) involves a substitution of the guanine by an adenine nucleotide base in IL17A gene promotor which plays a key role in regulation of cytokine transcription. The relation of IL17 polymorphisms however to psoriasis risk and response to methotrexate has not been previously studied in Egyptians. Objective To study the relation of IL17A (rs2275913 G>A) and IL17F (rs2397084 T>C) polymorphisms to psoriasis risk and assess their predictive role regarding response to methotrexate. Patients and methods The study was conducted in two phases. First, a case-control study including 100 patients with chronic plaque psoriasis and 100 healthy control patients was conducted for IL17A (rs2275913) and IL17F (rs2397084) polymorphisms by real-time PCR. Second, a cohort study was adopted where the patients with psoriasis were treated with methotrexate weekly intramuscularly (0.6 mg/kg) for 12 weeks and followed for clinical response. Results IL17F TT genotype was more frequent in patients (87%) than controls (68%), whereas TC genotype was more frequent in controls (32%) than patients (13%). TT genotype was associated with increased risk of psoriasis, whereas the TC allele was associated with a decreased risk. There was no significant difference regarding IL17A GG, GA, and AA genotype frequencies between patients and controls. Psoriasis area and severity index greater than or equal to 75% was achieved in 22 patients (73.3%) with the TT genotype and eight patients (26.7%) with TC genotype (P=0.019). Conclusion IL17F (rs2397084 T>C) TT genotype could be considered a susceptibility marker in Egyptian patients. Psoriatic patients with TT genotype and T allele of IL17F (rs2397084 T>C) are likely to show a better response to methotrexate.