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

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 (CBRblacks = 10.9 +/- 4.1 nmol/min mg) versus CBRwhites=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 NQOI*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 NQO1blacks[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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.