Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Abstract: Objective. Ankylosing spondylitis (AS) is one of the mostcommoncauses of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be>90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study’s purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. Methods. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: Results. The IL1 rs1800587, IL1rs16944 and IL1rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (2=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLAB2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Conclusion. Polymorphisms of IL1 rs1800587, IL1 rs16944 and IL1 rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS. Key words: ankylosing spondylitis, gene polymorphism, IL1 gene cluster, andHLA-B27 subtypes