title: Factors associated with paraoxonase genotypes and activity in a diverse, young, healthy population: the Coronary Artery Risk Development in Young Adults (CARDIA) study.
abstract: 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 < or =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 > or =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.
authors.affiliation: Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota Minneapolis, MN 55454, USA.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.forename: J Jeffery
authors.initials: JJ
authors.lastname: Carr
authors.forename: Ogechika
authors.initials: O
authors.lastname: Alozie
authors.forename: Michael W
authors.initials: MW
authors.lastname: Steffes
authors.forename: Poonguzhali
authors.initials: P
authors.lastname: Kailash
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Hayes
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
mesh_terms: D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D044383:Black People; D001786:Blood Glucose / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000208:ethnology; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D044465:White People
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human