Polymorphisms within Genes Coding for IL‐17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis

Abstract

IL-17A and IL-17F together with their coreceptor (IL-17RA/RC) were reported to play a significant role in the pathogenesis of spondyloarthritis. The group of axial spondyloarthritis comprises ankylosing spondylitis (AS), a rheumatic disease characterized by chronic inflammation of the joints in the spine. This study is aimed at investigating <i>IL-17A</i>, <i>IL-17F</i>, <i>IL-17RA</i>, and <i>IL-17RC</i> polymorphisms as potential biomarkers of disease susceptibility, clinical parameters, and anti-TNF treatment outcome in a cohort of Polish ankylosing spondylitis patients. In total, 328 subjects, including 138 AS patients and 190 healthy volunteers, participated in the study. Genotyping of <i>IL-17A</i> rs2275913 (G/A), <i>IL-17F</i> rs763780 (A/G), <i>IL-17RA</i> rs4819554 (A/G), and <i>IL-17RC</i> rs708567 (G/A) was performed on real-time PCR instrument using LightSNiP assays. No significant differences were revealed in genotype and allele distribution between patients and controls despite the association of the <i>IL-17RC</i> rs708567 <i>AA</i> homozygosity with the earlier onset of the disease. Moreover, some relationships between <i>IL-17F</i> rs763780 and <i>IL-17RA</i> rs4819554 polymorphisms with clinical parameters related to the disease activity and anti-TNF treatment outcome were observed. <i>IL-17F</i> rs763780 G allele was found to be associated with high disease activity and BASDAI after 6 months and poor response to the treatment while higher VAS values were more common among <i>IL-17RA</i> rs4819554 G variant carriers. In conclusion, the <i>IL-17F</i> rs763780 polymorphism should be considered as a promising biomarker of disease activity and anti-TNF treatment outcome. The <i>IL-17RA</i> rs48419554 G allele may serve as a potential marker of disease severity in Polish AS patients.