Genetic polymorphism of CYP2D6 and CYP2C19 in East- and Southern African populations including psychiatric patients

被引:65
作者
Dandara, C
Masimirembwa, CM
Magimba, A
Sayi, J
Kaaya, S
Sommers, DK
Snyman, JR
Hasler, JA
机构
[1] Univ Zimbabwe, Dept Biochem, Harare, Zimbabwe
[2] Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania
[3] Univ Pretoria, Dept Pharmacol, ZA-0002 Pretoria, South Africa
关键词
African populations; genetic polymorphism;
D O I
10.1007/s002280100282
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives: The study was carried out to investigate the distribution of cytochrome P450 2D6 (CYP2B6) 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 CYP2B6 (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 metaboliser frequency of 2.3% (2/88) in Tanzanian psychiatric patients, 1.9% (2/106) in Tanzanian healthy controls and 3.6% (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 metabolisers (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. Conclusion: 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.
引用
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页码:11 / 17
页数:7
相关论文
共 35 条
[1]  
Aklillu E, 1996, J PHARMACOL EXP THER, V278, P441
[2]   Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population [J].
Bathum, L ;
Skjelbo, E ;
Mutabingwa, TK ;
Madsen, H ;
Horder, M ;
Brosen, K .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1999, 48 (03) :395-401
[3]  
BERTILSSON L, 1995, ADV DRUG METABOLISM, P85
[4]   Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions [J].
Bertz, RJ ;
Granneman, GR .
CLINICAL PHARMACOKINETICS, 1997, 32 (03) :210-258
[5]  
Checkoway H, 1998, NEUROTOXICOLOGY, V19, P635
[6]  
Christensen PM, 1998, PHARMACOGENETICS, V8, P473
[7]  
DEMORAIS SMF, 1994, MOL PHARMACOL, V46, P594
[8]  
DEMORAIS SMF, 1994, J BIOL CHEM, V269, P15419
[9]   Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians [J].
Droll, K ;
Bruce-Mensah, K ;
Otton, SV ;
Gaedigk, A ;
Sellers, EM ;
Tyndale, RF .
PHARMACOGENETICS, 1998, 8 (04) :325-333
[10]   Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil [J].
Fidock, DA ;
Wellems, TE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10931-10936