A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study

Objective: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, but there is limited information about the genetic contribution to atherosclerosis in this population. Therefore, we examined the association between selected genetic polymorphisms and coronary atherosclerosis in patients with RA. Methods: Genotypes for single-nucleotide polymorphisms (SNPs) in 152 candidate genes linked with autoimmune or cardiovascular risk were measured in 140 patients with RA. The association between the presence of coronary artery calcium (CAC) and SNP allele frequency was assessed by logistic regression with adjustment for age, sex, and race. To adjust for multiple comparisons, a false discovery rate (FDR) threshold was set at 20%. Results: Patients with RA were 54 +/- 11 years old and predominantly Caucasian (89%) and female (69%). CAC was present in 70 patients (50%). A variant in rs2073618 that encodes an Asn3Lys missense substitution in the osteoprotegerin gene (OPG, TNFRSF11B) was significantly associated with the presence of CAC (OR = 4.09, p < 0.00026) and withstands FDR correction. Conclusion: Our results suggest that a polymorphism of the TNFRSF11B gene, which encodes osteoprotegerin, is associated with the presence of coronary atherosclerosis in patients with RA. Replication of this finding in independent validation cohorts will be of interest.