Association of medicaons and rheumatoid arthritis susceptibility polymorphism with lipid profiles in patients with rheumatoid arthritis

Abstract

Background/Purpose: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD), and though the mechanism is unknown, there are independent associations with RA-related factors (del Rincon I Arth Rheum 2005; Wolfe F, Arth Rheum 2008; Goodson Arth Rheum 2002). We examined whether single nucleotide polymorphisms (SNPs) linked with RA susceptibility and treatment are associated with low density lipoprotein (LDL) and triglyceride (TG) levels in subjects with RA. Methods: Patients (n=1362) enrolled in the prospective Veterans Affairs RA (VARA) registry were genotyped for multiple SNPs with DNA samples derived from whole blood. Genes and associated SNPs included: REL (rs10203477, rs842647, rs13031237, rs9309331); DDAH2 (rs15574), interleukin-10 (rs3024493, rs1800872, rs1800896); methylenetetrahydrofolate reductase (rs1801131, rs1801133); tumor necrosis factor/ lymphotoxin A (rs3093662, rs1800629, rs3093668); and tumor necrosis factor receptor associated factor 1 (rs1014529, rs1014530). Covariates included: patient characteristics (age, ethnicity, gender, body mass index [BMI], diabetes, smoking status, education); RA severity markers (anti-CCP and rheumatoid factor status, C reactive protein level); lipid-lowering agent use (statin, fibrate, bile acid sequestrant); and lipid profile data. Multivariate linear regression was performed to determine factors associated with TG and LDLs. A p-value <0.01 was deemed significant in the final model. Results: Factors associated with lower LDL level were age, diabetes, statin use, and the REL-related SNP (rs9309331), where the presence of CC conferred a 13 point lower LDL value compared to GG (see Table). The distribution of TG values required a lognormal transformation of the data, and results are interpretable as percentages relative to subjects without the described trait. For example, subjects using fibrates still demonstrated TG values 87% higher than subjects not taking fibrates, despite use of these agents. Factors associated with higher TG levels were Caucasian race, BMI, diabetes, smoking status, and fibrate use. There was an interaction term between diabetes and fibrate use that was associated with a decreased TG level. (Table Presented) Conclusion: RA subjects on statins demonstrate lower LDL compared to RA subjects not receiving statins, but this was not found for fibrate use and TGs (unless the subject was also diabetic). A possible connection between rs9309331 and LDL levels should be further investigated.