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 pa...
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doaj-8ca24a74d2b943ebbfe3abe377f170662020-11-24T21:05:55ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-02-011623885389410.3390/ijms16023885ijms16023885A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene StudyCecilia P. Chung0Joseph F. Solus1Annette Oeser2Chun Li3Paolo Raggi4Jeffrey R. Smith5C. Michael Stein6Departments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USADepartments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USADepartments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USABiostatistics, Vanderbilt University, Nashville, TN 37232, USAMazankowski Alberta Heart Institute, Department of Medicine, University of Alberta, Edmonton, AB T6G 2B7, CanadaDepartments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USADepartments of Medicine and Biostatistics, Vanderbilt University, Nashville, TN 37232, USAObjective: 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.http://www.mdpi.com/1422-0067/16/2/3885rheumatoid arthritisgenetic variationSNPatherosclerosisrs2073618 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cecilia P. Chung Joseph F. Solus Annette Oeser Chun Li Paolo Raggi Jeffrey R. Smith C. Michael Stein |
spellingShingle |
Cecilia P. Chung Joseph F. Solus Annette Oeser Chun Li Paolo Raggi Jeffrey R. Smith C. Michael Stein A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study International Journal of Molecular Sciences rheumatoid arthritis genetic variation SNP atherosclerosis rs2073618 |
author_facet |
Cecilia P. Chung Joseph F. Solus Annette Oeser Chun Li Paolo Raggi Jeffrey R. Smith C. Michael Stein |
author_sort |
Cecilia P. Chung |
title |
A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study |
title_short |
A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study |
title_full |
A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study |
title_fullStr |
A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study |
title_full_unstemmed |
A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study |
title_sort |
variant in the osteoprotegerin gene is associated with coronary atherosclerosis in patients with rheumatoid arthritis: results from a candidate gene study |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-02-01 |
description |
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. |
topic |
rheumatoid arthritis genetic variation SNP atherosclerosis rs2073618 |
url |
http://www.mdpi.com/1422-0067/16/2/3885 |
work_keys_str_mv |
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