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 b y 'classical' risk factors such as total cholesterol, LDL-cholesterol, smok ing, etc. Design The effect of the human serum paraoxonase (PON1) 192-genetic polymor phism on plasma lipid and lipoprotein concentrations and on PON1 activity a nd 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 th e 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 Belfas t also had significantly higher serum cholesterol, triglycerides, LDL-chole sterol, and apolipoprotein B, and significantly lower HDL-cholesterol and a polipoprotein A1, but these lipoprotein parameters were independent of the PON1 192-polymorphisms. PON1 activity towards paraoxon was significantly hi gher in the Belfast population than in Toulouse (median values: 179.7 vs. 1 29.4 nmol min(-1) mL(-1) serum, respectively; P < 0.05), which is consisten t with our finding of a greater prevalence of the R allele. The median seru m concentration of PON1 was 56.3 mu g mL(-1) in Belfast, which was signific antly 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 tha t populations at increased CHD risk have diminished serum PON1 concentratio n and an increased prevalence of the R allele of PON1. They are also consis tent with reports that the ability of PON1 to hydrolyse paraoxon is inverse ly related to its capacity to hydrolyse lipid-peroxides, and thus to its an tiatherogenic action.