MDR1 pharmacogenetics:: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity

被引:328
作者
Ameyaw, MM
Regateiro, F
Li, T
Liu, XH
Tariq, M
Mobarek, A
Thornton, N
Folayan, GO
Githang'a, J
Indalo, A
Ofori-Adjei, D
Price-Evans, DA
McLeod, HL
机构
[1] Univ Aberdeen, Dept Med & Therapeut, Inst Med Sci, Aberdeen, Scotland
[2] Univ Ghana, Sch Med, Ctr Trop Clin Pharmacol, Accra, Ghana
[3] Univ Coimbra, Fac Med, Dept Med Genet, Coimbra, Portugal
[4] W China Univ Med Sci, Chengdu 610041, Sichuan, Peoples R China
[5] Riyadh Armed Forces Hosp, Riyadh, Saudi Arabia
[6] Univ Nairobi, Kenyatta Natl Hosp, Nairobi, Kenya
来源
PHARMACOGENETICS | 2001年 / 11卷 / 03期
关键词
P-glycoprotein; ethnicity; single nucleotide polymorphism; MDR1;
D O I
10.1097/00008571-200104000-00005
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
P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications, It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake, individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy, To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian population (P < 0.0001), The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele, The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively), The high frequency of the C allele in the African group implies overexpression of PGP and map have important: therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin. Pharmacogenetics 11:217-221 (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:217 / 221
页数:5
相关论文
共 29 条
  • [1] Ameyaw M M, 2000, Hum Mutat, V16, P445, DOI 10.1002/1098-1004(200011)16:5<445::AID-HUMU13>3.0.CO
  • [2] 2-3
  • [3] Thiopurine methyltransferase alleles in British and Ghanaian populations
    Ameyaw, MM
    Collie-Duguid, ESR
    Powrie, RH
    Ofori-Adjei, D
    McLeod, HL
    [J]. HUMAN MOLECULAR GENETICS, 1999, 8 (02) : 367 - 370
  • [4] A family of drug transporters: The multidrug resistance-associated proteins
    Borst, P
    Evers, R
    Kool, M
    Wijnholds, J
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (16): : 1295 - 1302
  • [5] CAVALLISFORZA LL, 1996, HIST GEOGRAPHY HUMAN, P11
  • [6] CHEN CJ, 1990, J BIOL CHEM, V265, P506
  • [7] Choo EF, 2000, DRUG METAB DISPOS, V28, P655
  • [8] MULTIDRUG-RESISTANCE GENE (P-GLYCOPROTEIN) IS EXPRESSED BY ENDOTHELIAL-CELLS AT BLOOD-BRAIN BARRIER SITES
    CORDONCARDO, C
    OBRIEN, JP
    CASALS, D
    RITTMANGRAUER, L
    BIEDLER, JL
    MELAMED, MR
    BERTINO, JR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) : 695 - 698
  • [9] THE MDR1 GENE-PRODUCT, P-GLYCOPROTEIN, MEDIATES THE TRANSPORT OF THE CARDIAC GLYCOSIDE, DIGOXIN
    DELANNOY, IAM
    SILVERMAN, M
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 189 (01) : 551 - 557
  • [10] Elmore JG, 1998, CANCER-AM CANCER SOC, V83, P2509, DOI 10.1002/(SICI)1097-0142(19981215)83:12<2509::AID-CNCR15>3.0.CO