Lower prevalence of the debrisoquin oxidative poor metabolizer phenotype in American black versus white subjects.
Our objective was to determine whether there are differences in debrisoquin hydroxylase (P450IID6) activity between American black subjects and white subjects. Phenotype was assigned in a group of 586 unrelated white and black children with use of dextromethorphan as the substrate probe. Restriction fragment length polymorphism analysis of genomic deoxyribonucleic acid (DNA) was performed in a subset of subjects by use of a full length complementary DNA for P450IID6. Thirty-seven of 480 (7.7%) white children were poor metabolizers compared with 2 of 106 (1.9%) black children (p = 0.03). Among 41 white subjects and 18 black subjects, there were significant differences (p less than 0.05) in two XbaI DNA restriction fragments; the 44 kb fragment was more common and the 29 kb fragment was less common in black versus white extensive metabolizers. There is a lower prevalence of the debrisoquin poor metabolizer phenotype among American black persons, which could have implications for efficacy or toxicity of drugs metabolized by this enzyme, as well as for racial differences in the prevalence of diseases associated with the debrisoquin oxidative phenotype.
Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, TN 38105.
M V
MV
Relling
J
J
Cherrie
M J
MJ
Schell
W P
WP
Petros
W H
WH
Meyer
W E
WE
Evans
D044383:Black People; D002648:Child; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D003647:Debrisoquin / Q000378:metabolism*; D003915:Dextromethorphan / Q000378:metabolism / Q000652:urine; D003917:Dextrorphan / Q000652:urine; D005260:Female; D006801:Humans; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D044465:White People
D003917:Dextrorphan; D003915:Dextromethorphan; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin