Ogawa Kento, Suno Manabu, Shimizu Keiko, Yoshida Masatsugu, Awaya Toshio, Matsubara Kazuo, Shiono Hiroshi
Department of Legal Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Leg Med (Tokyo). 2003 Sep;5(3):132-8. doi: 10.1016/s1344-6223(03)00055-5.
Tailor-made medical treatment based on the polymorphism of genes encoding drug-metabolizing enzymes has been advocated and is being tried on an experimental basis at numerous centers. If DNA polymorphism analysis becomes routine in tailor-made medical treatment, it will be very useful in forensic identification. In this study, we determined the genotype frequencies of five p450 (CYP) isoform genes, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19 in 196 Japanese individuals to evaluate their forensic usefulness. These genes encode the most important enzymes among the CYP superfamily that metabolize clinically used drug. The frequency of each allele agreed well with those reported previously and their genotype frequencies did not deviate from those expected from Hardy-Weinberg equilibrium. CYP2C subfamilies such as CYP2C9 and CYP2C19 on chromosome 10 showed high sequence homology, as high as over 95% in the regions flanking polymorphic sites. Although 3240 genotype combinations of these five CYP isoform genes are theoretically possible, 101 combinations were detected in this study. The genotype frequencies of these five isoform genes excluded their linkage. The following two genotype combinations showed the highest frequency of 0.036: CYP1A2*1A/1A, CYP2D61/10, CYP2E11/1, CYP2C91/1 and CYP2C191/1 and CYP1A21A/1C, CYP2D61/10, CYP2E11/1, CYP2C91/1 and CYP2C191/*1. Thus, genotyping of CYP isoform genes should be useful in forensic identification.
基于药物代谢酶编码基因多态性的个体化医疗已得到提倡，并且在众多中心正处于实验尝试阶段。如果DNA多态性分析在个体化医疗中成为常规操作，那么它将在法医鉴定中非常有用。在本研究中，我们测定了196名日本个体中五个细胞色素P450（CYP）同工型基因CYP1A2、CYP2D6、CYP2E1、CYP2C9和CYP2C19的基因型频率，以评估它们在法医鉴定中的实用性。这些基因编码CYP超家族中代谢临床所用药物的最重要的酶。每个等位基因的频率与先前报道的频率吻合良好，并且它们的基因型频率未偏离哈迪-温伯格平衡预期的频率。位于10号染色体上的CYP2C亚家族，如CYP2C9和CYP2C19，显示出高度的序列同源性，在多态性位点侧翼区域高达95%以上。尽管这五个CYP同工型基因理论上可能有3240种基因型组合，但在本研究中检测到了101种组合。这五个同工型基因的基因型频率排除了它们之间的连锁关系。以下两种基因型组合的频率最高，为0.036：CYP1A2*1A/1A、CYP2D61/10、CYP2E11/1、CYP2C91/1和CYP2C191/1以及CYP1A21A/1C、CYP2D61/10、CYP2E11/1、CYP2C91/1和CYP2C191/*1。因此，CYP同工型基因的基因分型在法医鉴定中应该是有用的。
