S-mephenytoin hydroxylation phenotype and CYP2C19 genotype among ethiopians

被引:78
作者
Persson, I
Aklillu, E
Rodrigues, F
Bertilsson, L
IngelmanSundberg, M
机构
[1] KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS,S-17177 STOCKHOLM,SWEDEN
[2] UNIV ADDIS ABABA,FAC MED,ADDIS ABABA,ETHIOPIA
[3] HUDDINGE UNIV HOSP,KAROLINSKA INST,DIV CLIN PHARMACOL,DEPT MED LAB SCI & TECHNOL,S-14186 HUDDINGE,SWEDEN
来源
PHARMACOGENETICS | 1996年 / 6卷 / 06期
关键词
cytochrome P450; mephenytoin; omeprazole; proguanil; genotype; genetic polymorphism;
D O I
10.1097/00008571-199612000-00005
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The polymorphic metabolism of S-mephenytoin and the distribution of two known deleterious mutant CYP2C19 alleles was determined among 114 healthy unrelated black Ethiopians, Six subjects (5.2%) were poor metabolizers (PMs) of S-mephenytoin, The frequencies of the defective CYP2C19*2 (CYP2C19m1) and CYP2C19+3 (CYP2C19m2) alleles were 0.14 and 0.02, respectively, Three of the PMs were homozygous for the CYP2C19*2 allele and the remaining three PMs were heterozygous for both the CYP2C192 and CYP2C19*3 mutant alleles, It is concluded that the frequency of PMs for S-mephenytoin is similar in Ethiopians, Zimbabweans and Caucasians and that the CYP2C19*3 allele, for the first time identified in a black population, together with the CYP2C19*2 allele account for all of the defective CYP2C19 alleles among the Ethiopan PMs.
引用
收藏
页码:521 / 526
页数:6
相关论文
共 38 条
  • [1] ADEDOYIN A, 1994, PHARMACOGENETICS, V4, P27
  • [2] AKLILLU E, 1996, IN PRESS J PHARM EXP
  • [3] HYDROXYLATION POLYMORPHISMS OF DEBRISOQUINE AND MEPHENYTOIN IN EUROPEAN POPULATIONS
    ALVAN, G
    BECHTEL, P
    ISELIUS, L
    GUNDERTREMY, U
    [J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 39 (06) : 533 - 537
  • [4] SLOW OMEPRAZOLE METABOLIZERS ARE ALSO POOR S-MEPHENYTOIN HYDROXYLATORS
    ANDERSSON, T
    REGARDH, CG
    DAHLPUUSTINEN, ML
    BERTILSSON, L
    [J]. THERAPEUTIC DRUG MONITORING, 1990, 12 (04) : 415 - 416
  • [5] THE CYTOCHROME-P450 CYP2D6 ALLELIC VARIANT CYP2D6J AND RELATED POLYMORPHISMS IN A EUROPEAN POPULATION
    ARMSTRONG, M
    FAIRBROTHER, K
    IDLE, JR
    DALY, AK
    [J]. PHARMACOGENETICS, 1994, 4 (02): : 73 - 81
  • [6] IMPORTANCE OF GENETIC-FACTORS IN THE REGULATION OF DIAZEPAM METABOLISM - RELATIONSHIP TO S-MEPHENYTOIN, BUT NOT DEBRISOQUIN, HYDROXYLATION PHENOTYPE
    BERTILSSON, L
    HENTHORN, TK
    SANZ, E
    TYBRING, G
    SAWE, J
    VILLEN, T
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (04) : 348 - 355
  • [7] IN-VITRO PROGUANIL ACTIVATION TO CYCLOGUANIL BY HUMAN LIVER-MICROSOMES IS MEDIATED BY CYP3A ISOFORMS AS WELL AS BY S-MEPHENYTOIN HYDROXYLASE
    BIRKETT, DJ
    REES, D
    ANDERSSON, T
    GONZALEZ, FJ
    MINERS, JO
    VERONESE, ME
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1994, 37 (05) : 413 - 420
  • [8] PROGUANIL METABOLISM IS DETERMINED BY THE MEPHENYTOIN OXIDATION POLYMORPHISM IN VIETNAMESE LIVING IN DENMARK
    BROSEN, K
    SKJELBO, E
    FLACHS, H
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 36 (02) : 105 - 108
  • [9] A MULTIFAMILY STUDY ON THE RELATIONSHIP BETWEEN CYP2C19 GENOTYPE AND S-MEPHENYTOIN OXIDATION PHENOTYPE
    BROSEN, K
    DEMORAIS, SMF
    MEYER, UA
    GOLDSTEIN, JA
    [J]. PHARMACOGENETICS, 1995, 5 (05): : 312 - 317
  • [10] RECONSTRUCTION OF HUMAN-EVOLUTION - BRINGING TOGETHER GENETIC, ARCHAEOLOGICAL, AND LINGUISTIC DATA
    CAVALLISFORZA, LL
    PIAZZA, A
    MENOZZI, P
    MOUNTAIN, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (16) : 6002 - 6006