Yalcıntepe Sinem, Ozdemır Ozturk, Sılan Coskun, Ozen Filiz, Uludag Ahmet, Candan Ferhan, Sılan Fatma
Department of Medical Genetics, Faculty of Medicine, Canakkale Onsekiz Mart University, 17100, Canakkale, Turkey.
Department of Medical Genetics, Adana Numune Education and Research Hospital, Adana, Turkey.
Eur J Drug Metab Pharmacokinet. 2016 Jun;41(3):281-6. doi: 10.1007/s13318-015-0255-8. Epub 2015 Feb 3.
The cytochrome P450 2D6 (CYP2D6) is a cytochrome P450 enzyme involved in the oxidative biotransformation of the xenobiotics, carcinogens and various clinically important drugs. Patients are evaluated in three sub-groups of extensive (EM), intermediate (IM) and poor metabolizer (PM) phenotypes due to their drug-metabolising ability for the target CYP2D6 gene. Colchicine non-responsive FMF patients were prospectively genotyped for the major CYP2D6 alleles in the current study. Major CYP2D6 alleles of *1, *3, *4, *5, and *6 were genotyped for 30 responsive and 60 non-responsive FMF patients by multiplex PCR-based reverse-hybridization StripAssay and real-time PCR methods. DNA banks isolated from blood-EDTA were retrospectively used in the current patients and results were compared statistically. Increased CYP2D6 *4 and *6 allele frequencies were highly detected in the colchicine non-responsive FMF patients when compared to the responsive group. Results showed the frequencies of major CYP2D6 *1(wild), *3(2637A > delA), *4(G1934A), 5(total gene deletion) and 6(1707T del) alleles in 0.550, 0.042, 0.158, 0.025 and 0.225 for non-responder and 0.880 and 0.120 (CYP2D61 and 4) for the responder groups, respectively. Despite small sample size, this study suggests that there is an association between CYP2D64 and CYP2D66 alleles and drug intoxicants in colchicine non-responder FMF patients.
细胞色素P450 2D6（CYP2D6）是一种细胞色素P450酶，参与外源性物质、致癌物和各种临床上重要药物的氧化生物转化。由于患者对目标CYP2D6基因的药物代谢能力，他们被分为广泛代谢型（EM）、中间代谢型（IM）和慢代谢型（PM）三个亚组进行评估。在本研究中，对秋水仙碱无反应的家族性地中海热（FMF）患者进行了主要CYP2D6等位基因的前瞻性基因分型。通过基于多重PCR的反向杂交StripAssay和实时PCR方法，对30例有反应和60例无反应的FMF患者的主要CYP2D6等位基因*1、*3、4、5和6进行了基因分型。从血液乙二胺四乙酸（EDTA）中分离的DNA库被回顾性地用于当前患者，并对结果进行统计学比较。与有反应组相比，在秋水仙碱无反应的FMF患者中，CYP2D6 4和6等位基因频率显著增加。结果显示，无反应组中主要CYP2D6 1（野生型）、3（2637A＞delA）、4（G1934A）、5（全基因缺失）和6（1707T del）等位基因的频率分别为0.550、0.042、0.158、0.025和0.225，有反应组中为0.880和0.120（CYP2D61和4）。尽管样本量较小，但本研究表明，在秋水仙碱无反应的FMF患者中，CYP2D64和CYP2D66等位基因与药物中毒之间存在关联。
