title: Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations.
abstract: OBJECTIVE
  Cytochrome P450 2C19 (CYP2C19) and CYP2D6 are important xenobiotic metabolic enzymes and both show considerable genetic variability between Orientals and Caucasians. There are known marked heterogeneity in susceptibility to various cancers and hypertension among Chinese Mongolian, Hui and Han ethnic groups, but the molecular mechanisms are unknown. Our objective was to investigate the patterns of distribution of CYP2C19 and CYP2D6 polymorphisms among healthy Chinese subjects to determine whether any observed inter-ethnic variability might be worth further investigation as possible contributors to the known differences in disease prevalence.
  
  
  METHODS
  Blood samples were collected from 454 unrelated Chinese healthy subjects (214 Han, 111 Hui, 129 Mongolian) for genotyping analysis. The single nucleotide polymorphisms (SNPs) CYP2C19*2 (681G>A in exon 5), CYP2C19*3 (636G>A in exon 4) and CYP2D6*10 (188C>T in exon 1) were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
  
  
  CONCLUSIONS
  Significantly higher frequencies of the CYP2C19 poor metabolic genotypes were observed in Chinese Han (18·7%), Chinese Hui (25·0%) and Chinese Mongolian (10·9%) subjects than has been reported for Caucasians (1·7-3·0%, P < 0·01). The prevalent defective allele CYP2C19*2 occurred more frequently in both Chinese Hui (32·4%) and Han (29·7%) than in Chinese Mongolian (18·2%, P < 0·01) subjects. The CYP2C19*2 and CYP2C19*3 defective alleles were significantly more frequent in Chinese Han and Chinese Hui ethnic groups than have been reported for Caucasians (11·1-16·3% and 0-0·2%, P < 0·01). CYP2D6*1/*10 heterozygotes and CYP2D6*10/*10 homozygotes were observed more frequently in Chinese Han (43·1% and 27·2%), Hui (40·6% and 30·7%) and Mongolian subjects (31·3% and 9·6%, both P < 0·01) than have been reported for Caucasians (5·5% and 0·3%, P < 0·01). In Chinese Mongolians, the CYP2D6*10 allele occurred at a frequency (25·2%, P < 0·01) intermediate between those reported for Caucasians and the other two Chinese ethnic populations.
  
  
  CONCLUSIONS
  This is first report of interethnic differences in frequencies of functional CYP2C19 and CYP2D6 genes among Chinese Mongolian, Hui and Han populations. These differences may be important in explaining reported inter-ethnic differences in disease prevalence and response to drugs.
authors.affiliation: Department of Pharmacology, Basic Medical School, Beijing (Peking) University, Beijing, China.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Yin
authors.forename: Y-B
authors.initials: YB
authors.lastname: Ni
authors.forename: S-M
authors.initials: SM
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Lou
authors.forename: G-L
authors.initials: GL
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D054458:Amplified Fragment Length Polymorphism Analysis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics*; D001711:Biotransformation; D002681:China; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6