Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians.
Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians.
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DOI：
10.1097/00008571-199706000-00003
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发表时间：
1997-06
期刊：
影响因子：
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通讯作者：
R. McLellan;M. Oscarson;Janeric Seidegård;David A. Price Evans;Magnus Ingelman-Sundberg
中科院分区：
文献类型：
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作者：
R. McLellan;M. Oscarson;Janeric Seidegård;David A. Price Evans;Magnus Ingelman-Sundberg
多态性细胞色素P450 2D 6（CYP 2D 6）导致几种临床重要药物的代谢不良、广泛或超速，表现出明显的种族间差异。超快速代谢是由多拷贝的活性CYP 2D 6基因引起的，最近29%的埃塞俄比亚人群已被证明携带重复或多重复的CYP 2D 6基因，而在其他黑人、东方和欧洲人群中相应的频率为1- 2%。为了表征在相邻人群中具有多个CYP 2D 6拷贝的等位基因的分布，并表征沙特阿拉伯人中的CYP 2D基因座，使用限制性片段长度多态性（RFLP）分析和等位基因特异性聚合酶链反应（PCR）扩增对沙特阿拉伯人群的CYP 2D 6基因型进行了研究。在研究的101名沙特阿拉伯人中，21名受试者具有指示CYP 2D 6基因重复的EcoRI片段。相比之下，只有两个人是杂合子的缺失的整个基因（CYP 2D 6 *5）。CYP 2D 6 *4是高加索人中最常见的缺陷等位基因，其等位基因频率在沙特人群中仅为3.5%。另外两个等位基因，CYP 2D 6 *10和 *17，在某些人群中很常见，导致酶活性降低，仅在3.0%的低等位基因频率下发现。这些发现与早期的沙特阿拉伯表型研究一致，该研究报告了CYP 2D 6探针药物的低代谢率（1-2%）。总之，研究的沙特阿拉伯人口表现出非常少的缺陷等位基因和大量的受试者携带重复的CYP 2D 6基因，这意味着高度保守的功能CYP 2D 6基因可能是由于饮食的原因，并揭示沙特阿拉伯作为一个独特的人口相比，其他检查。
The polymorphic cytochrome P450 2D6 (CYP2D6) causing poor, extensive or ultrarapid metabolism of several clinically important drugs exhibits pronounced interethnic variation. Ultrarapid metabolism is caused by multiple copies of active CYP2D6 genes and recently 29% of an Ethiopian population has been shown to carry duplicated or multiduplicated CYP2D6 genes, whereas the corresponding frequency in other black, Oriental and European populations investigated is 1-2%. In order to characterize the distribution of alleles with multiple CYP2D6 copies in a neighbouring population and to characterize the CYP2D locus in general among Saudi Arabians, the CYP2D6 genotype of a Saudi Arabian population was examined using restriction fragment length polymorphism (RFLP) analysis and allele-specific polymerase chain reaction (PCR) amplification. Of 101 Saudi Arabians studied, 21 subjects had an EcoRI fragment indicative of CYP2D6 gene duplication. In contrast, only two individuals were heterozygous for a deletion of the whole gene (CYP2D6*5). The allele frequency of CYP2D6*4, the most common defective allele among Caucasians, was only 3.5% in the Saudi population. Two other alleles, CYP2D6*10 and *17, common in certain populations and which cause diminished enzyme activity, were found only at low allele frequencies of 3.0% each. These findings are in agreement with earlier Saudi Arabian phenotyping studies which reported a low frequency (1-2%) of poor metabolizers for CYP2D6 probe drugs. In conclusion, the Saudi Arabian population studied exhibited very few defective alleles and a large number of subjects carried duplicated CYP2D6 genes, implying a high conservation on functional CYP2D6 genes possibly due to dietary reasons and reveal the Saudi Arabians as an unique population in comparison with others examined.