Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis

Lisa A. Davis, Emily Whitfield, Grant W. Cannon, Roger K. Wolff, Dannette S. Johnson, Andreas M. Reimold, Gail S. Kerr, J. Steuart Richards, Ted R Mikuls, Liron Caplan

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numberket472
Pages (from-to)1014-1021
Number of pages8
JournalRheumatology (United Kingdom)
Volume53
Issue number6
DOIs
StatePublished - Jun 2014

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HDL Lipoproteins
LDL Lipoproteins
Single Nucleotide Polymorphism
Rheumatoid Arthritis
Lipids
Cardiovascular Diseases
amsonic acid
Genes
Non-Receptor Type 22 Protein Tyrosine Phosphatase
TNF Receptor-Associated Factor 1
STAT Transcription Factors
CTLA-4 Antigen
Hydroxymethylglutaryl-CoA Reductase Inhibitors
HLA-DRB1 Chains
Veterans
HLA Antigens
Interleukin-10
Glucocorticoids
Alcoholism
Registries

Keywords

  • Arthritis
  • Cholesterol
  • HDL
  • LDL
  • Polymorphism
  • Rheumatoid
  • Single nucleotide
  • Triglycerides

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Davis, L. A., Whitfield, E., Cannon, G. W., Wolff, R. K., Johnson, D. S., Reimold, A. M., ... Caplan, L. (2014). Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis. Rheumatology (United Kingdom), 53(6), 1014-1021. [ket472]. https://doi.org/10.1093/rheumatology/ket472

Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis. / Davis, Lisa A.; Whitfield, Emily; Cannon, Grant W.; Wolff, Roger K.; Johnson, Dannette S.; Reimold, Andreas M.; Kerr, Gail S.; Richards, J. Steuart; Mikuls, Ted R; Caplan, Liron.

In: Rheumatology (United Kingdom), Vol. 53, No. 6, ket472, 06.2014, p. 1014-1021.

Research output: Contribution to journalArticle

Davis, LA, Whitfield, E, Cannon, GW, Wolff, RK, Johnson, DS, Reimold, AM, Kerr, GS, Richards, JS, Mikuls, TR & Caplan, L 2014, 'Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis', Rheumatology (United Kingdom), vol. 53, no. 6, ket472, pp. 1014-1021. https://doi.org/10.1093/rheumatology/ket472
Davis, Lisa A. ; Whitfield, Emily ; Cannon, Grant W. ; Wolff, Roger K. ; Johnson, Dannette S. ; Reimold, Andreas M. ; Kerr, Gail S. ; Richards, J. Steuart ; Mikuls, Ted R ; Caplan, Liron. / Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis. In: Rheumatology (United Kingdom). 2014 ; Vol. 53, No. 6. pp. 1014-1021.
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abstract = "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.",
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AU - Whitfield, Emily

AU - Cannon, Grant W.

AU - Wolff, Roger K.

AU - Johnson, Dannette S.

AU - Reimold, Andreas M.

AU - Kerr, Gail S.

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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.

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KW - Cholesterol

KW - HDL

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KW - Polymorphism

KW - Rheumatoid

KW - Single nucleotide

KW - Triglycerides

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