CYP3A5 variant allele frequencies in Dutch Caucasians.
CYP3A5 variant allele frequencies in Dutch Caucasians.
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DOI：
10.1093/clinchem/48.10.1668
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发表时间：
2002-10
影响因子：
9.3
通讯作者：
R. V. van Schaik;I. P. van der heiden;J. N. van den Anker;J. Lindemans
中科院分区：
文献类型：
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作者：
R. V. van Schaik;I. P. van der heiden;J. N. van den Anker;J. Lindemans
细胞色素P450 3A （CYP3A）家族的酶负责目前50%的处方药的代谢。CYP3A5在有限的个体中表达。在大约70%的白种人中，CYP3A5基因表达缺失与基因多态性（CYP3A5*3）有关。在CYP3A5多态性表达个体中，CYP3A5可能占CYP3A总蛋白的50%，因此它可能在CYP3A介导的药物代谢变化中起主要作用。通过测序，已经鉴定出（Hustert等人）。药物基因学11:773-9;2001;Kuehl等人。Nat Genet 2001；27:383-91) CYP3A5的变异等位基因*2到*7。检测CYP3A5变异等位基因，并了解其在特定种族群体中的等位基因频率，对于建立筛选这些多态性以优化药物治疗的临床相关性至关重要。方法采用新开发的pcr -限制性片段长度多态性检测方法，对500名健康荷兰高加索献血者CYP3A5*2、*3、*4、*5、*6、*7等位基因进行频率检测。结果荷兰高加索人群中CYP3A5*3等位基因缺陷频率为91%，其次是CYP3A5*2（1%）和CYP3A5*6（0.1%）。CYP3A5*4、*5、*7等位基因未检出。结论基于CYP3A5*3等位基因的等位频率，在高加索人群中筛查CYP3A5*3等位基因具有重要意义。此外，对于CYP3A5*3等位基因杂合的个体，可以考虑筛选CYP3A5*2等位基因。CYP3A5*4、*5、*6和*7等位基因的等位频率较低，不支持初始筛选。
BACKGROUND Enzymes of the cytochrome P450 3A (CYP3A) family are responsible for the metabolism of >50% of currently prescribed drugs. CYP3A5 is expressed in a limited number of individuals. The absence of CYP3A5 expression in approximately 70% of Caucasians was recently correlated to a genetic polymorphism (CYP3A5*3). Because CYP3A5 may represent up to 50% of total CYP3A protein in individuals polymorphically expressing CYP3A5, it may have a major role in variation of CYP3A-mediated drug metabolism. Using sequencing, have been identified (Hustert et al. Pharmacogenetics 2001;11:773-9; Kuehl et al. Nat Genet 2001;27:383-91) variant alleles *2 through *7 for CYP3A5. Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in specific ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. METHODS In a group of 500 healthy Dutch Caucasian blood donors, we determined the allelic frequency of the CYP3A5*2, *3, *4, *5, *6, and *7 alleles by use of newly developed PCR-restriction fragment length polymorphism assays. RESULTS The frequency of the defective CYP3A5*3 allele in the Dutch Caucasian population was 91%, followed by the CYP3A5*2 (1%) and CYP3A5*6 (0.1%) alleles. The CYP3A5*4, *5, and *7 alleles were not detected. CONCLUSIONS On the basis of its allelic frequency, screening for the CYP3A5*3 allele in the Caucasian population is extremely relevant. In addition, screening for the CYP3A5*2 allele may be taken into consideration in individuals heterozygous for the CYP3A5*3 allele. The CYP3A5*4, *5, *6, and *7 alleles have low allelic frequencies that do not support initial screening.