Faculty of Medicine and Odonstomatology, University of Sciences, Techniques and Technologies of Bamako, Mali.
Center of Listening, Care, Animation and Counseling, Bamako, Mali.
Medicine (Baltimore). 2021 Jul 23;100(29):e26614. doi: 10.1097/MD.0000000000026614.
Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3745274 and CYP2B6 rs2279343 were represented by GA (60.24%) followed by TG (35.36%). We noted a strong linkage disequilibrium between CYP2B6 rs3745274 and CYP2B6 rs2279343 with D' = 0.91 and r2 = 0.9. The frequencies of the genotypic combinations were 43.5% (GT/AG), 37.3% (GG/AA) and 11.5% (TT/GG) in the combination of CYP2B6-rs3745274 and CYP2B6-rs2279343; 26.8% (GT/CC), 25.4%, (GT/CT), 17.2% and GG/CT in the combination CYP2B6-rs3745274-CYP3A4-rs2740574; 26.8% (AG/CC), 23.9% (AA/CC), 19.1% (AG/CT), and 11% (AA/CT) in the combination CYP2B6-rs2279343-CYP3A4-rs2740574, respectively. The most common triple genotype was GT/AG/CC with 24.9%, followed by GG/AA/CC with 23.9%, GT/AG/CT with 16.7%, and GG/AA/CT with 10%. Our results provide new insights into the distribution of these pharmacogenetically relevant genes in the Malian population. Moreover, these data will be useful for studies of individual genetic variability to drugs and genetic predisposition to diseases.
细胞色素 P450 酶在广泛的化合物（包括外源性化学物质、药物、激素和维生素）的 I 相生物转化过程中发挥核心作用。值得注意的是，这些酶高度多态性，根据遗传构成，个体可能具有酶活性受损。因此，鉴定这些基因中的遗传变异可以促进药物遗传学研究和多因素疾病的遗传易感性。我们使用 TaqMan 药物代谢基因分型检测方法对 209 名健康马里受试者进行 CYP2B6(rs3745274; rs2279343)和 CYP3A4(rs2740574)等位基因和基因型的频率检测。等位基因频率分别为 CYP2B6(rs3745274)37%；CYP2B6(rs2279343)38%；CYP3A4(rs2740574)75%。总体而言，马里观察到的频率与非洲除北非以外的报告频率具有统计学可比性。CYP2B6(rs3745274)和 CYP2B6(rs2279343)中的主要单倍型由 GA(60.24%)代表，其次是 TG(35.36%)。我们注意到 CYP2B6(rs3745274)和 CYP2B6(rs2279343)之间存在强连锁不平衡，D'=0.91，r2=0.9。CYP2B6-rs3745274 和 CYP2B6-rs2279343 基因型组合的频率分别为 43.5%(GT/AG)、37.3%(GG/AA)和 11.5%(TT/GG)；CYP2B6-rs3745274 和 CYP2B6-rs2279343 的组合中为 26.8%(GT/CC)、25.4%（GT/CT）、17.2%和 GG/CT；CYP2B6-rs3745274-CYP3A4-rs2740574 的组合中为 26.8%(AG/CC)、23.9%(AA/CC)、19.1%(AG/CT)和 11%（AA/CT）；CYP2B6-rs2279343-CYP3A4-rs2740574 的组合中分别为 11%（AA/CT）。最常见的三联基因型是 GT/AG/CC，占 24.9%，其次是 GG/AA/CC，占 23.9%，GT/AG/CT，占 16.7%，GG/AA/CT，占 10%。我们的结果为马里人群中这些药物遗传学相关基因的分布提供了新的见解。此外，这些数据将有助于研究个体遗传变异对药物的影响和疾病的遗传易感性。
