Background Rheumatoid arthritis (RA) is a disease characterised by joint inflammation, in addition RA patients often suffer from dyslipidemia and cardiovascular disease (CVD). Apolipoprotein E (APOE) genotypes are associated with lipid levels, cardiovascular disease and CRP levels in the general population. It is unknown whether APOE genotypes are associated with RA susceptibility or severity.
Objectives We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers.
Methods 945 RA patients and 1121 controls were genotyped for two APOE polymorphisms. Genotype frequencies were compared between patients and controls. 205 patients (baseline disease duration <4 years) had 10 year longitudinal data, with repeated assessments of CRP, erythrocyte sedimentation rate (ESR) and hand radiographs (van der Heijde Sharp scored (SHS)). We examined longitudinal associations between APOE genotypes and SHS, CRP and ESR, respectively. Lipid levels, carotid intima media thickness, carotid plaques, history of CVD were compared across genotypes in a cross sectional study of 136 patients. Analyses were adjusted for confounders, covariates and multiple testing.
Results We found a longitudinal linear association between APOE genotypes and radiographic joint damage. ɛ2 carriers had highest radiographic score, followed by ɛ3/ɛ3, and ɛ4 carriers had lowest score (Coefficient (95% CI): -0.43 (-0.74 - -0.12)p=0.007). The association remained significant after adjustment for age, gender, ACPA status, DMARD treatment and time. We also found an association with total cholesterol (TC) and low-density lipoproteins (LDL) (ɛ2 < ɛ3/ɛ3 < ɛ4, p=0.03 and p=0.02, TC and LDL respectively, Table). Associations remained significant in multivariate analyses, where adjustments were made for age, gender and statins. No association was found with RA susceptibility, CRP, ESR, or CVD markers.
Conclusions Joint damage can be viewed as cumulative inflammation over time, and our findings suggest that APOE genotypes are associated with joint damage in RA over a 10-year period. These findings are in accordance with a study by Toms et al which found an association between APOE genotypes and disease activity in RA (Journal of Rheumatology, 2011). In addition, our results indicate that APOE genotypes influence TC and LDL levels in RA patients which may promote atherosclerosis.
Disclosure of Interest None Declared
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