<p>Background: Ankylosing Spondylitis (AS) is a chronic autoinflammatory Spondyloar-thropathy (SpA) which is characterized by sacroiliitis, which progresses to the axial skeleton. It seems that non-Human Leukocyte Antigen (HLA) and also HLA-B27 are associated with the susceptibility and pathogenesis of the disease. The recent Genome-Wide Association Studies (GWASs) have reported intergenic rs6759298 to be associated with AS etiology. The aim of this study was investigation of the rs6759298 polymorphism in Iranian AS patients. In addition, probable correlations with clinical indices and manifestations were considered.<br /> Methods: This study included 403 patients with AS. The control group consisted of 506 healthy individuals who were matched for sex, age, and ethnicity with AS group. Genotyping of rs6759298 was determined using the Amplification-Refractory Muta-tion System-Polymerase Chain Reaction (ARMS-PCR).<br /> Results: The GG genotype and G allele were found to be significantly more prevalent in the patient group in comparison to the control group [(p=2&times;10^-6 and 7.44&times;10^-9; OR (95% CI) =2.16 (1.56-2.98) and 1.73 (1.43-2.08)], respectively.<br /> Conclusion: No associations were found between patients with three genotypes and any disease manifestations or clinical indices. This investigation confirmed a highly significant association of rs6759298 with disease susceptibility, with no effect on disease progress or clinical presentations. Since rs6759298 belongs to the 2p15 gene desert, further studies would elucidate the exact role of this polymorphism in the pathogenesis of AS.</p>