Arvanitidis Kostas, Ragia Georgia, Iordanidou Maria, Kyriaki Sofia, Xanthi Athanasia, Tavridou Anna, Manolopoulos Vangelis G
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Fundam Clin Pharmacol. 2007 Aug;21(4):419-26. doi: 10.1111/j.1472-8206.2007.00510.x.
The aim of the present study was to determine the prevalence of the most common allelic variants of the polymorphic cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 and to predict the genotype frequency for each polymorphism in the Greek population. DNA isolated from peripheral blood samples derived from 283 non-related Greek ethnic subjects was used to determine the frequency of CYP2D63, CYP2D64, CYP2C92, CYP2C93 and CYP3A53 allelic variants by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, CYP2C192 and CYP2C193 with allelic specific amplification (PCR-ASA), and CYP2D62 (gene duplications) by long PCR analysis. The allelic frequencies (out of a total of 566 alleles) for CYP2D63 and CYP2D64, were 2.3% and 17.8%, respectively, while gene duplications (CYP2D62) were found in 7.4% of the subjects tested. For CYP2C92 and CYP2C93 polymorphisms the allelic frequencies were 12.9% and 8.13% respectively. For CYP2C19, the 2 polymorphism was present at an allelic frequency of 13.1%, while no subjects were found carrying the CYP2C193 allele. Finally, the CYP3A53 allele was abundantly present in the Greek population with an allelic frequency of 94.4%. Overall our results show that the frequencies of the common defective allelic variants of CYP2C9, CYP2C19 and CYP3A5 in Greek subjects are similar to those reported for several other Caucasian populations. Finally, a high prevalence of CYP2D6 gene duplication among Greeks was found, a finding that strengthens the idea that a South/North gradient exists in the occurrence of CYP2D6 ultrarapid metabolizers in European populations.
本研究的目的是确定多态性细胞色素P450（CYP）酶CYP2D6、CYP2C9、CYP2C19和CYP3A5最常见等位基因变体的流行情况，并预测希腊人群中每种多态性的基因型频率。从283名无亲缘关系的希腊族裔受试者的外周血样本中分离出的DNA，用于通过聚合酶链反应（PCR）-限制性片段长度多态性方法确定CYP2D63、CYP2D64、CYP2C92、CYP2C93和CYP3A53等位基因变体的频率，通过等位基因特异性扩增（PCR-ASA）确定CYP2C192和CYP2C193，通过长PCR分析确定CYP2D62（基因重复）。CYP2D63和CYP2D64的等位基因频率（在总共566个等位基因中）分别为2.3%和17.8%，而在7.4%的受试对象中发现了基因重复（CYP2D62）。对于CYP2C92和CYP2C93多态性，等位基因频率分别为12.9%和8.13%。对于CYP2C19，2多态性的等位基因频率为13.1%，而未发现携带CYP2C193等位基因的受试者。最后，CYP3A53等位基因在希腊人群中大量存在，等位基因频率为94.4%。总体而言，我们的结果表明，希腊受试者中CYP2C9、CYP2C19和CYP3A5常见缺陷等位基因变体的频率与其他几个白种人群体报告的频率相似。最后，发现希腊人中CYP2D6基因重复的发生率很高，这一发现强化了欧洲人群中CYP2D6超快代谢者的出现存在南/北梯度的观点。
