AB0006 Genetic Susceptibility Variants for Rheumatoid Arthritis do not Associate with Radiological Progression in Early Active Disease: Table 1.
Authors: I.C. Scott, J. Walker, J. Quist, S.L. Spain, R. Tan, S. Steer, Y. Okada, S. Raychaudhuri, A.P. Cope, C.M. Lewis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Several studies have tested the hypothesis that RA susceptibility variants associate with radiological progression. Their findings are often not replicated; additionally they have examined only a proportion of risk loci and evaluated each locus separately, despite limited power. Two recent meta-analyses of genome-wide association studies have expanded the number of genetic loci and HLA amino acid polymorphisms associated with RA susceptibility [1, 2]. Our aim was to establish if these variants correlated with radiological progression in early active RA patients enrolled to a clinical trial. We evaluated their association both individually and cumulatively, using a weighted genetic risk score (wGRS) combining risk loci. <h3>Objectives</h3> To establish if genetic predictors of RA susceptibility also associate with radiological progression in early active RA. <h3>Methods</h3> We evaluated 421 RA patients previously enrolled to the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial. Hand/feet radiographs were read for modified Larsen scores every 6 months for 2 years. We evaluated the association of validated genetic risk variants (69 SNPs, 17 four-digit <i>HLA-DRB1</i> alleles and polymorphisms in 6 HLA amino acid positions) with log-transformed Larsen scores over time using a linear mixed-effects model. Log<sub>e</sub> (Larsen score + 1) was the response variable. Time, treatment, age, disease duration, ACPA status, genotype and a genotype*time interaction, were the fixed-effects predictor variables. Genotype was coded additively. All β-estimates were back-transformed to the original Larsen scale. The genotype*time β provided information on the annual increase in Larsen score per risk allele copy relative to the reference genotype; <i>P</i>-values for this term provided information on the variant9s role in radiological progression. We assessed the association between a wGRS incorporating susceptibility SNPs and radiological progression by replacing the linear model9s genotype term with a wGRS. Ethical approval was obtained; all patients provided consent. <h3>Results</h3> Two SNPs, one <i>HLA-DRB1</i> allele and two HLA-DRβ1 protein amino acid polymorphisms had <i>P</i>-values &lt;0.05 (Table). None attained Bonferroni corrected significance. No association was seen between a wGRS and Larsen score progression (<i>P</i>=0.0680). <h3>Conclusions</h3> RA susceptibility loci did not have a clinically relevant association with radiological progression in European ancestry, early, active RA patients recruited to this trial. This suggests the genetic architectures of RA susceptibility and severity differ. <h3>References</h3> Okada Y et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2013; [Epub ahead of print]. Raychaudhuri S et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 2012;44:291-6. <h3>Acknowledgements</h3> Arthritis Research UK (Grant Reference Number 19739 to ICS); National Institute for Health Research (NIHR) Biomedical Research Centre at Guy9s and St Thomas9 NHS Foundation Trust in partnership with King9s College London. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5018