THU0474 Association of Il4, IL4R and IL8RB Gene Polymorphisms with the Risk of Developing Rheumatoid Arthritis

Background Candidate gene association studies have consistently demonstrated that the dysregulation of the immune responses underlying rheumatoid arthritis (RA) are influenced by single nucleotide polymorphisms (SNPs) in immuno-modulating genes. Objectives The aim of this study was to test whether 50 potentially functional SNPs in 17 immuno-modulating genes (IL4, IL4R, IL5, IL8, IL8RA, IL8RB, IL10, IL10RA, IL12A, IL12B, IL13, IL16, IFNG, IFNGR2, CCR5, MIF, and VEGFA) are associated with the risk of RA. Methods We genotyped selected SNPs in 1239 RA patients and 1229 controls using KASPar® assays (LGC Genomics). Five percent of samples were included as quality control duplicates. Results We found that carriers of the IL4 rs2070874T, IL4 rs2243290A, IL4 rs2243250T and IL4 rs2243268C alleles and the IL8RB rs2230054C/C and IL8RB rs1126580G/G genotypes had a significantly increased risk of RA (OR=1.37, 95%CI 1.11-1.71, P=0.004; OR=1.33, 95%CI 1.07-1.65, P=0.009; OR=1.32, 95%CI 1.07-1.63, P=0.01; OR=1.25, 95%CI 1.01-1.56, P=0.04; OR=1.31, 95%CI 1.05-1.63, P=0.01 and OR=1.36, 95%CI 1.10-1.69, P=0.002, respectively) whereas carriers of the IL10 rs3024509C/C genotype showed a significantly decreased risk for the disease (OR=0.26, 95%CI 0.09-0.75, P=0.007). Haplotype analysis also revealed that carriers of the IL4 TTCAT and IL8RB CG haplotypes had a significantly increased risk of RA (OR=1.28, 95%CI 1.05-1.56, P=0.016 and OR=1.24, 95%CI 1.09-1.41, P=0.001, respectively) whereas carriers of the IL4R GG haplotype had a decreased risk of developing the disease (OR=0.78, 95%CI 0.63-0-95, P=0.016). Interestingly, the association of the IL4 rs2243250 polymorphism was confirmed in a well-powered meta-analysis including 7150 individuals (OR=1.186, 95%CI 1.07-1.31, P=0.0010) although we failed to show a relationship between this promoter variant and the expression levels of IL4 mRNA (P=0.51). Finally, SNP-SNP interaction analysis suggested that the IL8RB rs1126580 and IL8RB rs2230054 SNPs also influence on risk of RA through interactions with the CCR5 rs2734648 SNP (P=0.028 and 0.026, respectively). Conclusions These findings strongly suggest that genetic variants within IL4, IL8RB and IL4R genes may play a role in determining the risk for RA. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5176