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; chi(2) = 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 mu g mL(-1) in Belfast, which was significantly lower (P < 0.005) than the level of 71 mu g 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.