Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population
Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population
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DOI：
10.2217/14622416.7.6.831
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发表时间：
2006-09-01
期刊：
影响因子：
2.1
通讯作者：
He, Lin
中科院分区：
文献类型：
--
作者：
Du, Jing;Xing, Qinghe;He, Lin
目的：细胞色素P450 3A 4（CYP 3A 4）是肝脏和肠道的主要代谢酶。它参与目前使用的所有药物的50%以上的代谢。本研究旨在确定CYP 3A 4变异性的遗传基础。研究方法：采用直接测序法对60例健康中国人（汉族20例，畲族30例，侗族10例）的CYP 3A 4基因进行了单核苷酸多态性（SNP）分析。对这些样本进行了连锁不平衡、单倍型推断和Hardy-Weinberg平衡分析。结果：在CYP 3A 4基因上共发现20个SNPs，其中11个为已知SNPs，9个为新发现SNPs。我们研究中检测到的已知SNP为CYP 3A 4 *1B、CYP 3A 4 *1G、CYP 3A 4 *10、CYP 3A 4 *13、CYP 3A 4 *14、CYP 3A 4 *15、CYP 3A 4 *17、CYP 3A 4 *18、rs3091339、rs3091430和rs 28371761，新SNP为-658 A -> C、G27 A（E10 K）、T48 A、G14284 A（G167 D）、A15623 G（N191 D）、C15635 A（L196 I）、T15656 C（F203 L）、G14199 A（内含子5）和C15566 T（内含子6）。我们的样本中发现的等位基因频率从1- 37%不等。在CYP 3A 4基因中检测到的新的SNPs表明中国人群与其他人群相比具有不同的等位基因频率模式。结论：CYP 3A 4基因存在多个SNP位点。研究CYP 3A 4基因的遗传变异对了解基因型与表型的关系具有重要意义。
Objectives: Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and intestine. It is involved in the metabolism of over 50% of all drugs currently in use. The present study was designed to determine the genetic basis of CYP3A4 variability. Methods: Single nucleoticle polymorphism (SNP) analysis of the CYP3A4 gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. Results: A total of 20 SNPs were found in the CYP3A4 gene, including 11 known SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B, CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18, rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A -> C, G27A (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196l), T15656C (F203L), G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that the Chinese population has different patterns of allele frequency compared with other populations. Conclusion: Several SNPs were detected in the CYP3A4 gene. The study of genetic variants in CYP3A4 may have an important significance for the understanding of genotype and phenotype relationships.