Elmachad Mustapha, Elkabbaj Driss, Elkerch Fatiha, Laarabi Fatima Zahra, Barkat Amina, Oualim Zouhir, Sefiani Abdelaziz
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco.
Genet Test Mol Biomarkers. 2012 Jun;16(6):644-7. doi: 10.1089/gtmb.2011.0240. Epub 2012 Feb 3.
The cytochromes P450 are a superfamily of oxidative enzymes, which are implicated in the metabolism of a large number of endogenous substances as well as exogenous chemicals. The cytochrome P450 (CYP3A5) appears to play an important role in drug metabolism activity. The most frequent mutation in the CYP3A5 gene, affecting its activity, consists of a G6986A transition within intron 3. In this study, we determined the allelic frequency of CYP3A53 in a Moroccan population, consisting of 108 individuals including 10 renal transplant patients. About 8.33% (9/108) of the subjects were homozygous wild-type (CYP3A51/1), 37.04% (40/108) were heterozygous (CYP3A51/3), and 54.63% (59/108) were homozygous (CYP3A53/3). Therefore, CYP3A53 variant was the most frequent allele detected at 73.15%. In the second part of this work, we assessed the influence of the CYP3A5 polymorphism on tacrolimus doses required for 10 renal transplant patients who are receiving tacrolimus as immunosuppressive therapy. Our results showed that, during the first 3 months after kidney transplantation, the tacrolimus daily requirements for heterozygous patients (CYP3A5*3/1) were higher compared with homozygous patients (CYP3A53/3) (0.133 ± 0.026 vs. 0.21 ± 0.037 mg/kg/day). After the third month the difference was also observed, whereby the mean of tacrolimus daily requirements for patients with CYP3A53/3 and CYP3A51/*3 was 0.053 ± 0.013 and 0.08 ± 0.014 mg/kg/day, respectively. This first study in Morocco provides genetic data related to the frequency of genetic polymorphisms of CYP3A5 and opens the perspective to develop other pharmacogenetic studies.
细胞色素P450是一类氧化酶超家族，参与大量内源性物质以及外源性化学物质的代谢。细胞色素P450（CYP3A5）似乎在药物代谢活性中发挥重要作用。CYP3A5基因中影响其活性的最常见突变是内含子3内的G6986A转换。在本研究中，我们测定了摩洛哥人群中CYP3A53的等位基因频率，该人群由108名个体组成，其中包括10名肾移植患者。约8.33%（9/108）的受试者为纯合野生型（CYP3A51/1），37.04%（40/108）为杂合子（CYP3A51/3），54.63%（59/108）为纯合子（CYP3A53/3）。因此，CYP3A53变体是检测到的最常见等位基因，频率为73.15%。在本研究的第二部分，我们评估了CYP3A5基因多态性对10名接受他克莫司作为免疫抑制治疗的肾移植患者所需他克莫司剂量的影响。我们的结果表明，在肾移植后的前3个月，杂合子患者（CYP3A5*3/1）的他克莫司每日需求量高于纯合子患者（CYP3A53/3）（0.133±0.026 vs.0.21±0.037mg/kg/天）。第三个月后也观察到了差异，CYP3A53/3和CYP3A51/*3患者的他克莫司每日需求量平均值分别为0.053±0.013和0.08±0.014mg/kg/天。这项在摩洛哥进行的首次研究提供了与CYP3A5基因多态性频率相关的遗传数据，并为开展其他药物遗传学研究开辟了前景。
