Higher activity of polymorphic NADH:quinone oxidoreductase in liver cytosols from blacks compared to whites.

Covarrubias VG, Lakhman SS, Forrest A, Relling MV, Blanco JG.

In human liver, the two-electron reduction of quinone compounds, such as menadione is catalyzed by cytosolic carbonyl reductase (CBR) and NADH: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+/-5.0nmol/minmg), and white donors (11.4+/-6.6nmol/minmg; p=0.208). In addition, both groups presented similar levels of CBR activities (CBR_blacks=10.9+/-4.1nmol/minmg) versus CBR_whites=10.5+/-5.8nmol/minmg; p=0.708). In contrast, blacks showed higher NQO1 activities (two-fold) than whites (NQO1_blacks)=2.1+/-3.0nmol/minmg versus NQO1_whites=0.9+/-1.6nmol/minmg, 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+/-1.7nmol/minmg versus NQO1_{whites[NQO1*1/*2+NQO1*2/*2]}=0.5+/-0.7nmol/minmg, p<0.01), but not in blacks (NQO1_{blacks[NQO1*1/*1]}=2.6+/-3.4nmol/minmg versus NQO1_{blacks[NQO1*1/*2]}=1.1+/-1.2nmol/minmg, p=0.134). Our findings pinpoint the presence of significant interethnic differences in polymorphic hepatic NQO1 activity.

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