Paraoxonase activity in two healthy populations with differing rates of coronary heart disease.

Background: The rate of coronary heart disease is over three-fold greater in Belfast than in Toulouse and the excess risk cannot be totally explained by 'classical' risk factors such as total cholesterol, LDL-cholesterol, smoking, etc.

Design: The effect of the human serum paraoxonase (PON1) 192-genetic polymorphism on plasma lipid and lipoprotein concentrations and on PON1 activity and concentration was investigated in 186 randomly selected healthy subjects from Toulouse and 165 from Belfast.

Results: The frequency of the R allele of PON1, which has been related to the risk of coronary heart disease, was significantly higher in Belfast (0.33) than in Toulouse (0.24; chi2 = 7.229, P = 0.0072). Subjects from Belfast also had significantly higher serum cholesterol, triglycerides, LDL-cholesterol, and apolipoprotein B, and significantly lower HDL-cholesterol and apolipoprotein A1, but these lipoprotein parameters were independent of the PON1 192-polymorphisms. PON1 activity towards paraoxon was significantly higher in the Belfast population than in Toulouse (median values: 179.7 vs. 129.4 nmol min-1 mL-1 serum, respectively; P < 0.05), which is consistent with our finding of a greater prevalence of the R allele. The median serum concentration of PON1 was 56.3 microgram mL-1 in Belfast, which was significantly lower (P < 0.005) than the level of 71 microgram mL-1 in Toulouse.

Conclusions: Our results thus provide further support for the hypothesis that populations at increased CHD risk have diminished serum PON1 concentration and an increased prevalence of the R allele of PON1. They are also consistent with reports that the ability of PON1 to hydrolyse paraoxon is inversely related to its capacity to hydrolyse lipid-peroxides, and thus to its antiatherogenic action.