Association of rheumatoid arthritis susceptibility  gene with lipid profiles in patients with  rheumatoid arthritis.
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- and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified CharlsonDeyo comorbidity 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.


CONCLUSIONS
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.
Lisa A
LA
Davis
Emily
E
Whitfield
Grant W
GW
Cannon
Roger K
RK
Wolff
Dannette S
DS
Johnson
Andreas M
AM
Reimold
Gail S
GS
Kerr
J Steuart
JS
Richards
Ted R
TR
Mikuls
Liron
L
Caplan
D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology / Q000235:genetics; D005260:Female; D020573:Genes, rel; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides