Isaac A O, Wetkos D D, Oche A O, Godwin I, Phyllis K, John A C
Department of Clinical Pharmacy and Pharmacy Practice, Jos University Teaching Hospital, University of Jos, Jos, Nigeria.
Department of Clinical Pharmacy and Pharmacy Practice, African Centre for Phytomedicine Research, University of Jos, Jos, Nigeria.
Niger J Clin Pract. 2020 Dec;23(12):1736-1743. doi: 10.4103/njcp.njcp_348_20.
Africans exhibit great diversity in cytochrome P450 2B6 isoenzyme (CYP2B6), the major enzyme in efavirenz metabolism.
We examined the frequency of two functional single nucleotide polymorphisms (SNPs) of the CYP2B6 pharmacogene in HIV-infected Nigerians on efavirenz-based antiretroviral therapy. The potential implications of the SNPs for HIV therapy were discussed.
A cross-sectional study conducted from July 2018 to December 2018 in a tertiary health facility in Nigeria. A random sample of a clinic cohort of HIV-infected adult Nigerians of different ethnicities was characterized for two key SNPs; CYP2B6:516G>, and CYP2B6:983T > C, defining the alleles CYP2B66 and CYP2B618, respectively. Hardy-Weinberg equilibrium was calculated to evaluate the genotype frequency distribution.
Genotyping was successful for 262 (83%) of the 316 study participants. Of those with genotype results, mean age was 41 ± 8 years and 182 (69.5%) were female. The CYP2B6:516 G/G (extensive metabolizers), CYP2B6:516 G/T (intermediate metabolizers), and CYP2B6:516 T/T (poor metabolizers) genotype frequency was 35.9%, 46.6%, and 17.6%, respectively. Also, 88.9% and 11.1% of participants were carriers of the CYP2B6:983 T/T and CYP2B6:983 T/C (poor metabolizers) genotypes, respectively. There were no gender or age-related differences in the genotype distribution. The CYP2B6:516G >T allele frequencies showed no significant deviations from the Hardy-Weinberg equilibrium (P = 0.66).
The intermediate metabolizer genotype was more common than the extensive and poor metabolizer genotypes in our study sample. We recommended further studies to investigate the risk of efavirenz underexposure and overexposure in carries of the extensive and poor metabolizer genotypes respectively in our patient population.
非洲人在细胞色素P450 2B6同工酶（CYP2B6）方面表现出极大的多样性，CYP2B6是依法韦仑代谢的主要酶。
我们研究了接受基于依法韦仑的抗逆转录病毒治疗的尼日利亚HIV感染者中CYP2B6药物基因的两种功能性单核苷酸多态性（SNP）的频率。讨论了这些SNP对HIV治疗的潜在影响。
2018年7月至2018年12月在尼日利亚一家三级医疗机构进行了一项横断面研究。对不同种族的感染HIV的成年尼日利亚人临床队列的随机样本进行了两种关键SNP的特征分析；CYP2B6:516G>，和CYP2B6:983T>C，分别定义等位基因CYP2B66和CYP2B618。计算哈迪-温伯格平衡以评估基因型频率分布。
316名研究参与者中有262名（83%）成功进行了基因分型。在有基因型结果的参与者中，平均年龄为41±8岁，182名（69.5%）为女性。CYP2B6:516 G/G（广泛代谢者）、CYP2B6:516 G/T（中间代谢者）和CYP2B6:516 T/T（慢代谢者）基因型频率分别为35.9%、46.6%和17.6%。此外，88.9%和11.1%的参与者分别是CYP2B6:983 T/T和CYP2B6:983 T/C（慢代谢者）基因型的携带者。基因型分布在性别或年龄方面没有差异。CYP2B6:516G>T等位基因频率与哈迪-温伯格平衡无显著偏差（P = 0.66）。
在我们的研究样本中，中间代谢者基因型比广泛代谢者和慢代谢者基因型更常见。我们建议进一步研究，分别调查我们患者群体中广泛代谢者和慢代谢者基因型携带者依法韦仑暴露不足和暴露过量的风险。
