Novel DNA sequence variations of cytochrome P450 genes in the Han Chinese population
Novel DNA sequence variations of cytochrome P450 genes in the Han Chinese population
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DOI：
10.2217/14622416.10.3.359
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发表时间：
2009-03-01
期刊：
影响因子：
2.1
通讯作者：
Chen, Yuan-Tsong
中科院分区：
文献类型：
--
作者：
Wang, Hui-Hung;Liao, Yie-Wen;Chen, Yuan-Tsong
目的：细胞色素P450是一种重要的单加氧酶，负责多种结构多样的化合物的代谢。本研究的目的是系统研究中国汉族人群中与药物代谢相关的14个细胞色素P450基因的DNA序列变异。材料与方法：对23例受试者的这14个基因进行测序，并测定其等位基因频率。结果：共发现312个基因变异，其中80个（25.6%）为新变异。这些新的变体包括67个非编码变体，4个同义变体和9个非同义变体。在这些变异体中，CYP 2 E1内含子6的3 '侧翼位点的11个核苷酸插入（c.968-77_-76 insGATGGGTGGAT）具有最高的等位基因频率，为0.565。预计这些新变体中共有16种具有潜在的功能性后果;然而，其中只有c. CYP 2C 18中的1299 T>A和c.- 498 C>A在CYP 2D 6中的频率达到4.9%。结论：本研究建立了中国汉族人群细胞色素P450基因的遗传数据库，并提示了这个重要基因家族的遗传多样性。
Aim: Cytochrome P450 is an important monooxygenase responsible for the metabolism of a large variety of structurally diverse compounds. The aim of this study was to systematically investigate the DNA sequence variations in 14 cytochrome P450 genes relevant to drug metabolism in the Han Chinese population. Materials & methods: We sequenced these 14 genes in 23 subjects and determined the allele frequencies. Results: We identified a total of 312 genetic variants, which included 80 (25.6%) novel variants. These novel variants included 67 noncoding variants, four synonymous and nine nonsynonymous variants. Among these variants, an 11-nucleotide insertion in the 3'-flanking site of intron 6 in CYP2E1 (c.968-77_-76insGATGGGTGGAT) had the highest allele frequency of 0.565. A total of 16 of these novel variants were predicted to have potential functional consequences; however, among them only c.-1299T>A in CYP2C18 and c.-498C>A in CYP2D6 reached a frequency of 4.9%. Conclusions: This study establishes a genetic database of cytochrome P450 genes in the Han Chinese population and suggests further genetic diversity throughout this important gene family.