The Cyp2b6 Gene Polymorphism and Phenotypic Correlation of Efavirenz-Based Combination Therapy Among the Niger Delta Ethnic Population: Implications in Modern Pharmacogenomics

Purpose: DNA polymorphism describes the difference between individuals, groups, or ethnicities, races, etc., in terms of their DNA sequences or phenotypes as relates to drug metabolism. Using predictive genotyping of drug-metabolizing genes, we can develop individuals' drug therapies that are less toxic and more effective. The main aim of the study was to evaluate genotype-phenotype-based correlation and incidence of genetic polymorphism of efavirenz blood levels among HIV/AIDS patients of the Niger Delta population. Methods: A study questionnaire was designed to obtained patients' data, blood samples were obtained, plasma was separated from the serum using a centrifuge for 5 minutes at 4000 rpm for HPLC analysis, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis was conducted using Bsrl endonuclease enzyme to digest the PCR amplicons. Standard efavirenz was used at 0.5, 1, 2, 4, 16 mg/L to construct a calibration curve. Data were analyzed with SPSS software using chi-square test at p-value <0.5 and Microsoft excel 2013, while PCR and RFLP results were obtained after 1% Agarose gel electrophoresis, respectively. Results: Phenotypic results showed that the participants had different efavirenz plasma concentrations. Six subjects (12%) had efavirenz plasma levels below 0.10 mg/L, considered ultra-rapid metabolizers (UMs), 22 (44%) 0.10 mg/L to 0.90 mg/L, classified as extensive metabolizers (EMs), 19 (38%) had 1.0 to 3.9 mg/L and were noted as intermediate metabolizers (IM), while 3 (6%) subjects showed efavirenz plasma levels from 4.0 mg/L to 6.0 mg/L, categorized as poor metabolizers (PM). RFLP results showed more than half of the population (56%) with a homozygous wild-type gene with CYP2B6*1*1 allele, 38% were CYP2B6*1*6 (heterozygous mutant) allele and 6% had homozygous mutant gene (CYP2B6*6*6 allele). Out of the 15 male subjects among the 50 patients that participated in the study, 8% were UM, 12% EM, 14% IM while no PM was observed, on the contrary, out of the 35 females participated in the study, 4% were observed as UM, 32% EM, 24% IM, while 6% were PM. Conclusion: There was no significant difference (p < 0.05) between genotype and phenotype data for CYP2B6 polymorphism, among the HIV/AIDS patients that participated in this study. Genetic polymorphism of the CYP2B6 gene is prevalent among HIV/AIDs patients in the Niger Delta ethnic population on efavirenz-based HAART treatment, as the population having homozygous mutant gene or PM are >1% (6%).