Savino Maria, Seripa Davide, Gallo Antonietta P, Garrubba Maria, D'Onofrio Grazia, Bizzarro Alessandra, Paroni Giulia, Paris Francesco, Mecocci Patrizia, Masullo Carlo, Pilotto Alberto, Santini Stefano A
Laboratory of Clinical Chemistry, Department of Clinical Pathology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
Clin Lab. 2011;57(11-12):887-93.
Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs.
An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele 2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D62A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer.
A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320).
The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.
近期对细胞色素P450（CYP）2D6单等位基因*2A的研究报告了其与药物治疗反应的关联。然而，通过基于高通量的技术可以获得更多的基因数据。本研究的目的是对CYP2D6基因多态性进行高通量分析，以评估其在识别对CYP2D6代谢药物有反应/无反应患者方面的有效性。
还尝试将我们的结果与先前通过CYP2D6等位基因2A标准分析获得的结果进行比较。对60份先前已进行CYP2D6等位基因2A基因分型、接受过CYP2D6代谢药物治疗的患者的血液样本，使用AutoGenomics INFINITI分析仪上的AutoGenomics INFINITI CYP4502D6-I检测法分析CYP2D6基因多态性。
在有反应的患者中观察到突变等位基因的频率高于无反应的患者（75.38%对43.48%；p = 0.015）。因此，CYP2D6突变等位基因的存在与对CYP2D6代谢药物的反应相关（优势比=4.044（1.348 - 12.154））。在等位基因*2A的分布上未观察到差异（p = 0.320）。
相对于CYP2D6等位基因*2A的标准分析，CYP2D6基因多态性的高通量基因分析能更好地区分有反应者/无反应者。CYP2D6的高通量基因检测可能有助于识别对CYP2D6代谢药物有不同临床反应的患者。
