Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype.
The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize the CYP2D6 substrate debrisoquine with 59% of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20% in Caucasians. This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6 gene mutations analysed for in this study. As many as 7% poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6 alleles. The majority among the group of poor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2D locus to that of Zimbabweans rather than to that of Ethiopians. The defective alleles CYP2D6*3, *4, *5 and *6 were found at low frequencies (0%, 1%, 6%, 0%, respectively), whereas the CYP2D6*17 allele causing an enzyme with altered specificity was common (allele frequency = 17%). It is concluded that the CYP2D6 genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates.
Wennerholm
A
A
Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, Sweden. agneta.wennerholm@labtek.ki.se
Johansson
I
I
Massele
A Y
AY
Lande
M
M
Alm
C
C
Aden-Abdi
Y
Y
Dahl
M L
ML
Ingelman-Sundberg
M
M
Bertilsson
L
L
Gustafsson
L L
LL
D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D003647:Debrisoquin / Q000493:pharmacokinetics*; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D013636:Tanzania
D017931:DNA Primers; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin