Topić E, Stefanović M, Nikolić V, Zoricić I, Ivanisević A M, Zuntar I
Clinical Institute of Chemistry, School of Medicine, University of Zagreb & Sestre milosrdnice University Hospital, Croatia.
Clin Chem Lab Med. 1998 Aug;36(8):655-8. doi: 10.1515/CCLM.1998.116.
The mutant of CYP2D63 allele with A2637 deletion in exon 5 and the mutant of CYP2D64 allele G1934-->A, splice site defect are among the most common polymorphic alleles of CYP2D6 gene, resulting in a decreased or no activity of CYP isoenzyme. In this study, a reliable polymerase chain reaction-restriction fragment length polymorphism method for identification of CYP2D63 and CYP2D64 alleles was used to investigate the genotype and phenotype prevalence in the groups of normal controls, and of cirrhosis and cancer patients. The results showed none of 36 controls genotyped for 2D63 and 2D64 allele to have the 2D63 allele with frameshift mutation in exon 5, while 33% (n=12) were found to bear the 2D64 allele with G to A mutation at the intron 3-exon 4 junction. In breast cancer patients (n=35) genotyped for 2D63 and 2D64 alleles, none with 2D63 allele was found either, but 60% (n=18) were found to bear the 2D64 allele. In patients with head and neck squamous cell cancer, there was only one subject with 2D63 allele and he was heterozygous. Among them, as many as ten (40%) patients were found to bear 2D64 allele. In the cirrhosis group, none of the patients was found to have the 2D63 allele, while the CYP2D64 allele was found in 23% (n=6) patients. The phenotype predicted according to the genotype was as follows: in the control group, 3% of individuals were identified as poor metabolizers, 70% as extensive metabolizers, and 27% as heterozygote extensive metabolizers. In the group of breast cancer, 7% of the patients were identified as poor metabolizer, 57% as extensive metabolizer and 36% as phenotype. In squamous cell cancer and cirrhosis patients, the incidence of poor metabolizer was zero, and of heterozygotes extensive metabolizer 42% and 31%, respectively.
细胞色素P450 2D6（CYP2D6）基因第5外显子存在A2637缺失的CYP2D63等位基因突变体以及G1934→A的CYP2D64等位基因突变体（剪接位点缺陷）是CYP2D6基因最常见的多态性等位基因，可导致CYP同工酶活性降低或丧失。在本研究中，采用一种可靠的聚合酶链反应-限制性片段长度多态性方法来鉴定CYP2D63和CYP2D64等位基因，以调查正常对照组、肝硬化患者组和癌症患者组的基因型和表型流行情况。结果显示，在36例检测CYP2D63和CYP2D64等位基因的对照组中，无人携带第5外显子发生移码突变的CYP2D63等位基因，而33%（n = 12）的个体携带内含子3-外显子4连接处发生G到A突变的CYP2D64等位基因。在35例检测CYP2D63和CYP2D64等位基因的乳腺癌患者中，也无人携带CYP2D63等位基因，但60%（n = 18）的患者携带CYP2D64等位基因。在头颈部鳞状细胞癌患者中，仅1例携带CYP2D63等位基因，且为杂合子。其中，多达10例（40%）患者携带CYP2D64等位基因。在肝硬化组中，未发现患者携带CYP2D63等位基因，而23%（n = 6）的患者携带CYP2D64等位基因。根据基因型预测的表型如下：在对照组中，3%的个体被鉴定为慢代谢者，70%为快代谢者，27%为杂合子快代谢者。在乳腺癌组中，7%的患者被鉴定为慢代谢者，57%为快代谢者，36%为特定表型。在鳞状细胞癌和肝硬化患者中，慢代谢者的发生率为零，杂合子快代谢者的发生率分别为42%和31%。
