Paraoxonase status in coronary heart disease - Are activity and concentration more important than genotype?

Human serum paraoxonase (PON1) hydrolyzes oxidized lipids in low density li poprotein (LDL) and could therefore retard the development of atheroscleros is. In keeping with this hypothesis, several case-control studies have show n a relationship between the presence of coronary heart disease (CHD) and p olymorphisms at amino acid positions 55 and 192 of PON1, which we associate d with a decreased capacity of PON1 to protect LDL against the accumulation of lipid peroxides, but some other studies have not. However, the PON1 pol ymorphisms are only 1 factor in determining the activity and concentration of the enzyme. Only 3 of the previous 18 studies directly determined PON1 a ctivity and concentration. Therefore, we studied PON1 activity, concentrati on, and gene distribution in 417 subjects with angiographically proven CHD and in 282 control subjects. We found that PON1 activity and concentration were significantly lower in subjects with CHD than in control subjects (act ivity to paraoxon 122.8 [3.3 to 802.8] versus 214.6 [26.3 to 620.8] nmol . min(-1) . mL(-1), P<0.001; concentration 71.6 [11.4 to 489.3] versus 89.1 [ 16.8 to 527.4] <mu>g/mL, P<0.001). There were no differences in the PON1-55 and -192 polymorphisms or clusterin concentration between patients with CH D and control subjects. These results indicate that lower PON1 activity and concentration and, therefore, the reduced ability to prevent LDL lipid per oxidation may be more important in determining the presence of CHD than par aoxonase genetic polymorphisms.