Paraoxonase gene polymorphisms and coronary reactivity in young healthy men

This study examined the relationships between paraoxonase genotypes, corona ry artery reactivity, and indices of low-density lipoprotein oxidation in h ealthy men. Impairment in coronary flow reserve, as assessed by positron em ission tomography, is associated with lipoprotein oxidation, which is affec ted by high-density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme. Forty-nine healthy men (mean age 35 +/- 4 years) were divided by p araoxonase genotype into low (Q192/Q192, or M55/M55, M55/L55) and high-acti ve (R192/Q192, R192/R192, or L55/L55) groups and related to the myocardial blood flow, to the susceptibility of low-density lipoprotein to oxidation, and the autoantibody titer against oxidized low-density lipoprotein. The bl ood flow was measured by positron emission tomography at rest and during ad enosine infusion. The low-active Q192/Q192 genotype was associated with hig her resting blood flow corrected for rate-pressure product compared to the high-active R192/R192 and R192/Q192 genotypes (P=0.011). The blood flow sti mulated by adenosine was not significantly different in the low- and high-a ctive genotype groups. Paraoxonase genotypes had no effect on low density l ipoprotein susceptibility to oxidation or autoantibody formation against ox idized low-density lipoprotein. Genotypes of paraoxonase may not clearly co ntribute to the early changes in coronary reactivity. Coronary vasomotor to ne at rest appears to be modulated by paraoxonase R/Q192 polymorphism throu gh mechanism(s) unrelated to low-density lipoprotein oxidation.