Higher activity of polymorphic NAD(P)H:quinone oxidoreductase in liver cytosols from blacks compared to whites

Abstract

In human liver, the two-electron reduction of quinone compounds, such as menadione is catalyzed by cytosolic carbonyl reductase (CBR) and NAD(P)H:quinone oxidoreductase (NQO1) activities. We assessed the relative contributions of CBR and NQO1 activities to the total menadione reducing capacity in liver cytosols from black ( n = 31) and white donors ( n = 63). Maximal menadione reductase activities did not differ between black (13.0 ± 5.0 nmol/min mg), and white donors (11.4 ± 6.6 nmol/min mg; p = 0.208). In addition, both groups presented similar levels of CBR activities (CBR blacks = 10.9 ± 4.1 nmol/min mg) versus CBR whites = 10.5 ± 5.8 nmol/min mg; p = 0.708). In contrast, blacks showed higher NQO1 activities (two-fold) than whites (NQO1 blacks = 2.1 ± 3.0 nmol/min mg versus NQO1 whites = 0.9 ± 1.6 nmol/min mg, p < 0.01). To further explore this disparity, we tested whether NQO1 activity was associated with the common NQO1 * 2 genetic polymorphism by using paired DNA samples for genotyping. Cytosolic NQO1 activities differed significantly by NQO1 genotype status in whites (NQO1 whites[ NQO1*1/*1] = 1.3 ± 1.7 nmol/min mg versus NQO1 whites[ NQO1*1/*2+NQO1*2/*2] = 0.5 ± 0.7 nmol/min mg, p < 0.01), but not in blacks (NQO1 blacks[ NQO1*1/*1] = 2.6 ± 3.4 nmol/min mg versus NQO1 blacks[ NQO1*1/*2] = 1.1 ± 1.2 nmol/min mg, p = 0.134). Our findings pinpoint the presence of significant interethnic differences in polymorphic hepatic NQO1 activity.