Genetic polymorphism of CYP2D6 and CYP2C19 in east- and southern African populations including psychiatric patients.
OBJECTIVE
The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2D6) and CYP2C19 genotype frequencies in three African populations and to compare these frequencies between healthy individuals and psychiatric patients.


METHODS
Three hundred and eighty-four subjects from South Africa (Venda), Tanzania, and Zimbabwe who consented to the study were genotyped for CYP2D6 (CYP2D6*1, *2, *3, *4, *5, and *17) and CYP2C19 (CYP2C19*1, *2, and *3) by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) techniques.


RESULTS
The genotypes for CYP2D6 predicted a poor metabolizer frequency of 2.3% (2/88) in Tanzanian psychiatric patients, 1.9% (2/106) in Tanzanian healthy controls and 2.6% (2/76) in the South African Venda. The low-activity CYP2D6*17 allele frequency was higher in psychiatric patients (30%, 53/176) than in healthy individuals (20%, 43/212) in Tanzanians. The frequencies for CYP2C19*2 genotypes were predictive of a low prevalence of poor metabolizers (PMs). The CYP2C19*3 allele was absent in the three populations studied. There was no difference in CYP2D6 or CYP2C19 PM genotype frequencies between psychiatric patients and healthy subjects.


CONCLUSIONS
The genotype results predict a low prevalence of people with deficient CYP2D6 and CYP2C19 activity among linguistically (Bantu) related populations of East and Southern Africa. The high frequency of the low-activity CYP2D6*17 allele predicts that the Bantu people have a reduced capacity to metabolise drugs that are CYP2D6 substrates.
Dandara
C
C
Department of Biochemistry, University of Zimbabwe, Harare, Zimbabwe.
Masimirembwa
C M
CM
Magimba
A
A
Sayi
J
J
Kaaya
S
S
Sommers
D K
DK
Snyman
J R
JR
Hasler
J A
JA
D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000353:Africa, Southern; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000201:enzymology* / Q000235:genetics*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6