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Population Differences in Major Functional Polymorphisms of Pharmacokinetics/pharmacodynamics-related Genes in Eastern Asians and Europeans: Implications in the Clinical Trials for Novel Drug Development

DRUG METABOLISM AND PHARMACOKINETICS, 2012, Vol.27 (1), p.9-54 [Peer Reviewed Journal]

2012 The Japanese Society for the Study of Xenobiotics ;ISSN: 1347-4367 ;EISSN: 1880-0920 ;DOI: 10.2133/dmpk.DMPK-11-RV-111 ;PMID: 22123129

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  • Title:
    Population Differences in Major Functional Polymorphisms of Pharmacokinetics/pharmacodynamics-related Genes in Eastern Asians and Europeans: Implications in the Clinical Trials for Novel Drug Development
  • Author: Kurose, Kouichi ; Sugiyama, Emiko ; Saito, Yoshiro
  • Subjects: allele frequencies ; Asian Continental Ancestry Group ; Biological Transport ; Biotransformation ; Clinical Trials as Topic ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Drugs, Investigational - pharmacokinetics ; Drugs, Investigational - pharmacology ; Drugs, Investigational - therapeutic use ; Eastern Asians ; European Continental Ancestry Group ; Europeans ; Gene Frequency ; genetic polymorphisms ; Humans ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Polymorphism, Genetic ; population differences
  • Is Part Of: DRUG METABOLISM AND PHARMACOKINETICS, 2012, Vol.27 (1), p.9-54
  • Description: Drug lag, recently discussed extensively in Japan, can be divided into two phases: clinical development time and application review time. The former factor is still an important problem that might be improved by promoting multi-regional clinical trials and considering the results from other similar populations with Japanese, such as Koreans and Chinese. In this review, we compare the allelic or genotype frequencies of 30 relatively common functional alleles mainly between Eastern Asians and Europeans as well as among 3 major populations in Eastern Asian countries, Japan, Korea, and China, in 12 pharmacokinetics (PK)/pharmacodynamics (PD)-related genes; CYP2C9 (*2 and *3), CYP2C19 (*2, *3 and *17), 13 CYP2D6 haplotypes including *4, *5 and *10, CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5, *6 and *7), GSTM1 and GSTT1 null genotypes, SLCO1B1 521T>C, ABCG2 421C>A, and HLA-A*31:01 and HLA-B* 58:01. In this review, differences in allele frequencies (AFs) or genotype frequencies (GFs) less than 0.1 (in the cases of highest AF (GF) >0.1) or less than 0.05 (in the cases of lowest AF (GF) <0.1) were regarded as similar. Between Eastern Asians and Europeans, AFs (or GFs) are regarded as being different for many alleles such as CYP2C9 (*2), CYP2C19 (*2, *3 and *17), CYP2D6 (*4 and *10), CYP3A5 (*3), UGT1A1 (*28 and *6), NAT2 (*5*7), GSTT1 null and ABCG2 421C>A. Among the 3 Eastern Asian populations, however, only AFs of CYP2C19*3, CYP2D6*10, HLA-A*31:01 and HLA- B*58:01 are regarded as dissimilar. For CYP2C19*3, the total functional impact on CYP2C19 could be small if the frequencies of the two null alleles CYP2C19*2 and *3 are combined. Regarding CYP2D6*10, frequency difference over 0.1 is observed only between Japanese and Chinese (0.147). Although environmental factors should be considered for PK/PD differences, we could propose that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms. On the other hand, AFs of the two HLA alleles important for cutaneous adverse drug reactions are diverse even among Eastern Asians and thus should be taken into account.
  • Publisher: England: Elsevier Ltd
  • Language: English;Japanese
  • Identifier: ISSN: 1347-4367
    EISSN: 1880-0920
    DOI: 10.2133/dmpk.DMPK-11-RV-111
    PMID: 22123129
  • Source: GFMER Free Medical Journals
    MEDLINE
    Alma/SFX Local Collection
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