TY - JOUR
T1 - Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis
AU - Davis, Lisa A.
AU - Whitfield, Emily
AU - Cannon, Grant W.
AU - Wolff, Roger K.
AU - Johnson, Dannette S.
AU - Reimold, Andreas M.
AU - Kerr, Gail S.
AU - Richards, J. Steuart
AU - Mikuls, Ted R.
AU - Caplan, Liron
N1 - Funding Information:
Funding: This work, including the genotyping, was supported by a Veterans Affairs Health Services Research and Development Grant (SHP 08-172) and the University of Colorado Denver, Division of Rheumatology. L.D. received support from the National Institutes of Health/ National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32 AR007534-24), National Institutes of Health Loan Repayment Award, the Rheumatology Research Foundation Rheumatology Scientist Development Award, Denver Health and Hospital Authority, the University of Colorado and the Colorado Clinical and Translational Science Institute. L.C. received support from a Veterans Affairs Health Services Research and Development Career Development Award (CDA 07-221). The funding sources had no role in the design, collection, analysis, interpretation of data, writing of the report or decision to submit this article for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or US government. All investigators participating in this research had access to all data. We declare that we (and our spouses, partners and children under 18 years of age) have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) this work, including employment, consultancies, stock ownership, honoraria, paid expert testimony, patents or patent applications and travel grants, within 5 years of beginning the work submitted.
PY - 2014/6
Y1 - 2014/6
N2 - Objective: RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects. Methods: Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethylglutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF-α and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified Charlson-Deyo co-morbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels. Results: The REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI. Conclusion: The REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry.
AB - Objective: RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects. Methods: Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethylglutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF-α and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified Charlson-Deyo co-morbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels. Results: The REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI. Conclusion: The REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry.
KW - Arthritis
KW - Cholesterol
KW - HDL
KW - LDL
KW - Polymorphism
KW - Rheumatoid
KW - Single nucleotide
KW - Triglycerides
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U2 - 10.1093/rheumatology/ket472
DO - 10.1093/rheumatology/ket472
M3 - Article
C2 - 24489016
AN - SCOPUS:84900800081
SN - 1462-0324
VL - 53
SP - 1014
EP - 1021
JO - Rheumatology (United Kingdom)
JF - Rheumatology (United Kingdom)
IS - 6
M1 - ket472
ER -