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Factors Associated with Paraoxonase Genotypes and Activity in a Diverse, Young, Healthy Population: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

¹ Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota Minneapolis, Minnesota; ² Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; ³ Department of Nutrition, University of Oslo, Oslo, Norway; ⁴ Division of Radiologic Sciences-Radiology, School of Medicine, Wake Forest University, Winston-Salem, North Carolina.

^aAddress correspondence to this author at: Division of Epidemiology and Community Health, University of Minnesota, School of Public Health, 1300 South Second St., Suite 300, Minneapolis, MN 55454. Fax 612 624 0315; e-mail jacobs{at}epi.umn.edu.

Background: Paraoxonase may mitigate oxidative damage and thus lower risk of macrovascular disease.

Methods: DNA samples from 2252 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were genotyped for the L55M and Q192R polymorphisms of the PON1 (paraoxonase 1) gene, and paraoxonase activity was measured in serum.

Results: The 192R (67.4% vs 29.7%) and 55L (80.0% vs 63.8%) alleles were more common in blacks vs whites. The Q192R locus was the strongest correlate of paraoxonase activity (100.4 nmol/mL/min greater in the 192RR than the 192QQ genotype). After adjustment for the Q192R locus, the L55M locus (12.7 nmol/mL/min difference between 55LL and 55MM) and race (6.6 nmol/mL/min difference between blacks and whites) were correlated with paraoxonase activity (P 0.0001), as were concentrations of HDL cholesterol (23.9 nmol/mL/min difference between highest and lowest quintiles), triglycerides (12.6 nmol/mL/min difference between highest and lowest quintiles), LDL cholesterol (8.2 nmol/mL/min difference between highest and lowest quintiles), smoking status (6.3 nmol/mL/min difference between current smokers of 15 cigarettes/day and never smokers), and glucose concentrations at the highest quintile (6.5 nmol/mL/min difference between highest and lowest quintiles in nondiabetic participants). There was no cross-sectional or longitudinal association between paraoxonase enzyme activity and coronary artery calcification (CAC), an early marker of cardiovascular disease, or its progression over 5 years.

Conclusions: Paraoxonase may not play an important role during the early pathogenesis of cardiovascular disease. However, associations with lipids and glucose suggest that paraoxonase may modify or react to macrovascular disease pathogenesis.