OP0088 STRATIFIED MEDICINE: GENETIC PREDICTORS OF RADIOGRAPHIC OUTCOME IN RHEUMATOID ARTHRITIS

Background Rheumatoid arthritis (RA) displays great heterogeneity between patients for susceptibility to developing erosions. Genetic variations within the HLA-DRB1 gene (the shared epitope (SE) and polymorphisms coding Valine at position 11) have been consistently associated with both radiographic outcome in RA.(1) However, associations of non-HLA markers are much less conclusive. Most studies looking outside HLA candidate very few replicated independent cohorts. Objectives: 1. Identify all single nucleotide (SNPs) that ever RA 2. To perform a replication study determine which these Norfolk Arthritis Register (NOAR), worldwide largest prospective cohort genetic data. Methods A systematic literature search was conducted as shown Figure Flow chart review. The register (NOAR) is large primary care-based inception diagnosed inflammatory polyarthritis. Patients were recruited baseline from 1989 followed up prospectively 20 years serial X-rays. Genome-wide genotyping performed on Illumina Human/Infinium Core Exome array imputed Minimac4 Haplotype Reference Consortium panel. Quality control resulted 7.5 million SNPs available each patient. identified extracted tested an association presence erosions (as longitudinal binary variable) using generalized estimating equation (GEE) model STATA/IC 14.0.in NOAR. Results total 2119 participants (2440 radiographs) data available. 66.2% female 33.3% anti-CCP positive. Median age onset 54.5 74.9% satisfied American College Rheumatology (ACR) 1987 criteria rheumatoid arthritis. 113 different literature. Of these, 102 successfully NOAR 91 deemed be based R 2 0.6. 14 found significantly (Table 1). Table severity *Significant results only; Dominant models used (Odds ratios displayed relation minor alleles) Gene Chromosome SNP (single polymorphism Odds ratio (95% CI) P value IL2RB rs743777 1.23 (1.01, 1.05) 0.0398 IL15 4 rs6821171 0.82 (0.67, 1.00) 0.0451 IL4 5 rs2243250 1.36 (1.08, 1.70) 0.0094 FOX03 6 rs12212067 0.75 (0.58, 0.97) 0.0278 OPG 8 rs2073618 0.79 (0.64, 0.98) 0.0295 TRAF1 9 rs10760130 1.33 (1.06, 1.65) 0.0118 rs10818488 1.32 1.64) 0.0141 rs2900180 (1.07, 1.61) 0.0079 IL4r 16 rs1805010 1.25 1.56) 0.0393 rs1805011 1.31 (1.03, 1.66) 0.0260 LGALS9 17 rs3763959 1.28 1.59) SOST rs4792909 1.34 (1.09, 0.0052 LILRA3 19 rs103294 0.80 (0.65, 0.0334 MMP9 rs11908352 0.70 (0.57, 0.85) 0.0005 Conclusion previously reported RA. only ~15% also showed NOAR, worldwide. Interestingly, rs2243250, located chromosome (IL4), small Egyptian cohort, has NOAR.(2) Current work consists assessing added clinical risk score predicting when combined clinical/serological/demographic markers. References [1]S. Viatte et al. , JAMA 313 1645-1656 (2015). [2]Y. M. Hussein, A. S. El-Shal, N. Rezk, Abdel Galil, Alzahrani, Cytokine 61 849-855 (2013). Disclosure Interests None declared.