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Int. J. Mol. Sci. 2015, 16(2), 3885-3894; doi:10.3390/ijms16023885

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

1
Departments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USA
2
Biostatistics, Vanderbilt University, Nashville, TN 37232, USA
3
Mazankowski Alberta Heart Institute, Department of Medicine, University of Alberta, Edmonton, AB T6G 2B7, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Michael Henein
Received: 14 December 2014 / Accepted: 6 February 2015 / Published: 11 February 2015
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
View Full-Text   |   Download PDF [708 KB, uploaded 11 February 2015]   |  

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. View Full-Text
Keywords: rheumatoid arthritis; genetic variation; SNP; atherosclerosis; rs2073618 rheumatoid arthritis; genetic variation; SNP; atherosclerosis; rs2073618
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Chung, C.P.; Solus, J.F.; Oeser, A.; Li, C.; Raggi, P.; Smith, J.R.; Stein, C.M. A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study. Int. J. Mol. Sci. 2015, 16, 3885-3894.

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