1 Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, University Hassan II , Casablanca, Morocco .
DNA Cell Biol. 2013 Oct;32(10):582-8. doi: 10.1089/dna.2013.2108. Epub 2013 Aug 9.
The multidrug resistance gene (MDR1) plays an important role in the transport of a wide range of drugs and elimination of xenobiotics from the body. Identification of polymorphisms and haplotypes in the MDR1 gene might not only help understand pharmacokinetics and pharmacodynamics of drugs, but also can help in the prediction of drug responses, toxicity, and side effects, especially, in the era of personalized medicine. We have analyzed the genotypic and haplotypic frequencies of the three most common single-nucleotide polymorphisms in the MDR1 gene in a sample of 100 unrelated healthy Moroccan subjects by polymerase chain reaction-restrictive fragment length polymorphism. The observed genotype frequencies were 43% for 1236CC, 49% for 1236CT, and 8% for 1236TT in exon 12; 49% for 2677GG, 47% for 2677GT, and 4% for 2677TT in exon 21; 39% for 3435CC, 51% 3435CT for 3435TT, and 10% for 3435TT in exon 26, respectively. We found that all polymorphisms were in Hardy-Weinberg equilibrium. Moderate linkage disequilibrium (LD) was observed between the three polymorphisms, the strongest LD in our study has been observed between C1236T and G2677T (D'=0.76; r(2)=0.45). We identified eight haplotypes, the most frequent were 1236C-2677G-3435C (53%), 1236T-2677T-3435T (21%), and 1236C-2677G-3435T (10%), respectively. Our findings might facilitate future studies on pharmacokinetics of P-glycoprotein substrate drugs and interindividual variability to drugs in Moroccan patients.
多药耐药基因（MDR1）在广泛的药物转运和外来物从体内消除中发挥重要作用。MDR1 基因的多态性和单倍型的鉴定不仅有助于了解药物的药代动力学和药效学，还可以帮助预测药物反应、毒性和副作用，特别是在个性化医学时代。我们通过聚合酶链反应-限制性片段长度多态性分析了 100 名无关的健康摩洛哥受试者中 MDR1 基因三个最常见的单核苷酸多态性的基因型和单倍型频率。在第 12 外显子中观察到的基因型频率为 1236CC 为 43%、1236CT 为 49%、1236TT 为 8%；在第 21 外显子中 2677GG 为 49%、2677GT 为 47%、2677TT 为 4%；在第 26 外显子中 3435CC 为 39%、3435CT 为 51%、3435TT 为 10%。我们发现所有多态性均处于哈迪-温伯格平衡状态。在三个多态性之间观察到中度连锁不平衡（LD），本研究中最强的 LD 存在于 C1236T 和 G2677T 之间（D'=0.76；r(2)=0.45）。我们鉴定了 8 种单倍型，最常见的是 1236C-2677G-3435C（53%）、1236T-2677T-3435T（21%）和 1236C-2677G-3435T（10%）。我们的研究结果可能有助于未来在摩洛哥患者中研究 P-糖蛋白底物药物的药代动力学和药物个体间变异性。
