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

Cecilia Chung,Paolo Raggi,C Stein,Jeffrey Smith,Chun Li,Joseph Solus,Annette Oeser

doi:10.3390/ijms16023885

Abstract

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.

Highlights

Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, with a two-fold increased risk in cardiovascular events [1]
The major finding of this study is that a polymorphism of the TNFRSF11B gene, which encodes osteoprotegerin, is associated with the presence of coronary atherosclerosis in patients with RA
Osteoprotegerin is a member of the TNF receptor family and acts as a soluble decoy receptor for receptor activator of nuclear factor KB ligand (RANKL) [14]

Summary

Introduction

Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, with a two-fold increased risk in cardiovascular events [1]. Traditional cardiovascular risk factors and inflammatory markers do not fully explain this increased risk [2,3,4,5]. Efforts to identify additional risk factors and improve our ability to predict cardiovascular risk in this patient population are important. Rheumatoid arthritis and atherosclerosis are chronic inflammatory conditions and both have significant genetic susceptibility. Of the risk in cardiovascular disease [6] there has been increasing interest in attempting to identify genetic markers of atherosclerosis in RA. We examined the association of these selected genetic polymorphisms with coronary atherosclerosis in patients with RA

Methods

Results

Conclusion