Relationship of age-related myocardial infarction risk and Gln/Arg 192 variants of the human paraoxonase1 gene: the REGICOR study

Atherosclerosis. 2001 Jun;156(2):443-9. doi: 10.1016/s0021-9150(00)00680-8.


Paraoxonase1 (PON1) seems to exert a major antioxidant effect by removing lipid-peroxidation products. A common polymorphism of the PON1 gene, the PON1-192 genetic polymorphism, modulates PON1 activity and has been related in some studies to coronary heart disease. Oxidized LDL is believed to play a crucial role in the pathogenesis of atherosclerosis and there are studies providing support for the oxidative stress theory of aging. We have conducted a case-control study to determine whether PON1 activity and PON1-192 genetic variants have a different impact on myocardial infarction (MI) risk among individuals stratified by tertiles of age distribution. PON1-192 genotypes and PON1 activity were determined in 280 consecutive MI patients and 396 control subjects. Serum PON1 activity levels were significantly higher in controls than in MI patients [226 U/l (159-351) vs. 216 U/l (146-298), median (interquartile range), P=0.005]. A decline of PON1 activity levels with advancing age in subjects carrying the low-activity QQ genotype was observed, particularly in MI patients. PON1 activity and age negatively correlated in MI patients but not in controls. In the entire population, middle-aged and older subjects showed MI risks of 1.89 (P=0.012) and 2.69 (P<0.001) respectively, compared with young subjects. These risks increased to 2.41 (P=0.016) and 4.39 (P<0.001), respectively, in QQ homozygotes in comparison with younger QQ homozygotes, decreased to 1.53 (P=0.314) and 2.08 (P=0.112), respectively, in QR heterozygotes, and also lowered to 1.95 (P=0.410) and 0.51 (P=0.508) in RR homozygotes who were middle-aged and older, respectively, compared with younger RR carriers. The effect of PON1-192 genotypes on the association of the older age-category and MI risk was gene-dosage related. PON1 activity decreases as a function of age in subjects homozygous for the Q allele. Age may also act on MI risk as a function of PON1-192 alleles. The risk of MI increases with advancing age, principally among subjects carrying the low-activity QQ genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Analysis of Variance
  • Aryldialkylphosphatase
  • Case-Control Studies
  • Chi-Square Distribution
  • Cohort Studies
  • Esterases / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Genotype
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / genetics
  • Polymorphism, Genetic*
  • Pregnancy
  • Reference Values
  • Risk Assessment
  • Risk Factors
  • Sex Distribution


  • Esterases
  • Aryldialkylphosphatase
  • PON1 protein, human