IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations
Yin, S. -J.; Ni, Y. -B.; Wang, S. -M.; Wang, X.; Lou, Y. -Q.; Zhang, G. -L.
关键词Cyp2c19 Cyp2d6 Genetic Polymorphism Han Hui Mainland Chinese Mongolian
刊名JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
2012-06-01
DOI10.1111/j.1365-2710.2011.01298.x
37期:3页:364-369
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]CYTOCHROME-P450 2D6 ; GENETIC POLYMORPHISMS ; POOR METABOLIZERS ; BREAST-CANCER ; ETHNIC-GROUPS ; 2C19 ; PHARMACOKINETICS ; TAMOXIFEN ; JAPANESE ; KAZAKH
英文摘要

What is known and 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 reactionrestriction fragment length polymorphism (PCR-RFLP) method. Results and Discussion: 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 (1.73.0%, 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 (11.116.3% and 00.2%, 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. What is new and 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.

语种英语
WOS记录号WOS:000304140200020
项目编号30973585 ; 91029747 ; 2009ZX09301-010 ; 2000A-1
资助机构National Natural Science Foundation of China ; &prime ; Major New Medicine Project&prime ; in Mega-projects of Science Research of China ; Beijing University Center for Human Disease Genomics
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56308
专题北京大学基础医学院_药理学系
作者单位Beijing Peking Univ, Hlth Sci Ctr, Basic Med Sch, Dept Pharmacol, Beijing 100191, Peoples R China
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GB/T 7714
Yin, S. -J.,Ni, Y. -B.,Wang, S. -M.,et al. Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations[J]. JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,2012,37(3):364-369.
APA Yin, S. -J.,Ni, Y. -B.,Wang, S. -M.,Wang, X.,Lou, Y. -Q.,&Zhang, G. -L..(2012).Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations.JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,37(3),364-369.
MLA Yin, S. -J.,et al."Differences in genotype and allele frequency distributions of polymorphic drug metabolizing enzymes CYP2C19 and CYP2D6 in mainland Chinese Mongolian, Hui and Han populations".JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS 37.3(2012):364-369.
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