Session Type: Abstract Submissions (ACR)
Paraoxonase 1 (PON1) is a high density lipoprotein (HDL) associated enzyme, which promotes the anti-oxidant and anti-inflammatory properties of HDL. PON1 polymorphisms and enzyme activity have previously been associated with cardiovascular (CV) events in the general population. Since abnormal HDL function has been proposed to contribute to CV risk in patients with rheumatoid arthritis (RA), the current work investigated the relationship of genetic and biochemical determinants of PON1 activity with carotid plaque as a surrogate marker of CV risk in RA patients.
PON1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 patients with RA. Fasting blood was collected for lipoprotein analysis, and PON1 activity was measured using paraoxon as the substrate. Genotyping for the PON1 Q192R polymorphism (SNP rs662) was done for all patients as described previously (Bhattacharyya et al. JAMA 2008). Lipoprotein cholesterol levels were measured by standard methods and traditional cardiovascular risk factors, medication use, and RA disease characteristics were assessed for all patients.
The PON1 genotype demonstrated a significant dose dependent association with PON1 activity (RR192 > QR192 > QQ192) (p<0.001). Compared to patients with either the PON1 QQ192 or QR192 genotype, patients with the RR192 genotype demonstrated decreased risk of carotid plaque in multivariate analysis controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol lowering medication use (p<0.05). Separate multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma PON1 activity with carotid plaque in RA patients. Lower plasma PON1 activity was associated with increased risk of carotid plaque (p <0.05).
The current work suggests a relationship between the genetic determinants and activity of PON1 with cardiovascular risk in RA patients as assessed by the presence or absence of carotid plaque. Further CV outcome studies may be warranted to determine if PON1 is a useful biomarker of CV risk in patients with RA.
Y. Y. Lee,
V. K. Ranganath,
M. B. Taylor,
M. A. McMahon,
S. T. Reddy,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-paraoxonase-1-gene-polymorphisms-and-enzyme-activity-with-carotid-plaque-in-rheumatoid-arthritis/