PARAOXONASE POLYMORPHISM MET-LEU54 IS ASSOCIATED WITH MODIFIED SERUM CONCENTRATIONS OF THE ENZYME - A POSSIBLE LINK BETWEEN THE PARAOXONASEGENE AND INCREASED RISK OF CARDIOVASCULAR-DISEASE IN DIABETES

Paraoxonase was identified as a genetic risk factor for cardiovascular disease (CVD) in recent studies focusing on a polymorphism affecting position 191, A second polymorphism of the paraoxonase gene affects po sition 54 and involves a methionine (M allele) to leucine CL allele) c hange. It was investigated in diabetic patients (n = 408) with and wit hout vascular disease, There were highly significant differences in pl asma concentrations and activities of paraoxonase between genotypes de fined by the 54 polymorphism MMAA, MLAA, LLAA; protein, 65.3 +/- 18.0, 77.9 +/- 18.0, 93.5 +/- 26.0 mu g/ml; P < 0.0001: activity (phenylace tate), 48.6 +/- 13.5, 64.1 +/- 14.5, 68.1 +/- 13.0 U/ml; P < 0.0001. T he 191 variant had little impact on paraoxonase concentrations, Homozy gosity for the L allele was an independent risk factor for CVD (odds r atio 1.98 (1.07-3.83); P = 0.031), A linkage disequilibrium (P < 0.000 1) was apparent between the mutations giving rise to leucine and argin ine at positions 54 and 191, respectively. The study underlines that s usceptibility to CVD correlates with high activity paraoxonase alleles , The 54 polymorphism would appear to be of central importance to para oxonase function by virtue of its association with modulated concentra tions, The fatter could explain the association between both the 54 an d 191 polymorphisms and CVD.