Unexpectedly higher diazoxon hydrolysis by serum paraoxonase-1 in coronary heart disease.

OBJECTIVES: Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD.

DESIGN & METHODS: Case- control study of 410 subjects with CHD and 274 controls. PON1 activity towards paraoxon and diazoxon, PON1 serum concentration and the PON1-55 and 192 polymorphisms were determined.

RESULTS: There were no differences in the distribution of the PON1-55 or PON1-192 genotypes between the CHD and controls, however, PON1 activity towards diazoxon (DIAZ) was significantly (+160%) higher in CHD. In the control population, DIAZ was significantly different between the PON1-192 genotypes in the order QQ > QR > RR (P < .001). However, in CHD the order was QQ > QR = RR. In CHD DIAZ was significantly higher in all the PON1-192 and 55 genotypes compared to controls. In both populations DIAZ was significantly different between the PON1-55 genotypes in the order LL > LM > MM (P < .001).

CONCLUSION: If this result can be replicated in other studies and/or with other PON1 substrates, there may be major diagnostic and mechanistic implications for the relationship of PON1 and CHD.