Allele and Genotype Frequencies of Cytochrome P450 2B6 516G>T Single Nucleotide Polymorphism in HIV-Negative and HIV-Infected Adult Nigerian Populations

Abstract

Polymorphisms in genes have been found in most enzymes involved in drug metabolism, especially in the cytochrome P450 (CYP) family with considerable ethnic differences in their frequencies. Single nucleotide polymorphisms (SNPs) are the major source of these genetic variations. CYP2B6 516G>T SNP found in both CYP2B6*6 and CYP2B6*9 alleles significantly reduces CYP2B6 protein expression and enzyme activity with important implications on the pharmacokinetics and pharmacodynamic outcomes of some clinically relevant drug substrates. This study determined the frequencies of CYP2B6 516G>T SNP in HIV-negative and HIV-infected adult Nigerian populations. Three hundred unrelated subjects (150 each of HIV-negative volunteers and HIV-infected patients) of different Nigerian ethnic groups residing in Ilorin and Ile-Ife and its environs, respectively, were recruited and genotyped for their CYP2B6 516G>T genetic status using real-time polymerase chain reaction. Differences in allele and genotype frequencies between both populations were tested using Pearson χ test. Minor allele frequency of 36.4% and genotype frequencies of 38.7% GG, 50.0% GT, 11.3% TT and a minor allele frequency of 37.0% and genotype frequencies of 42.0% GG, 42.0% GT, 16.0% TT were obtained for the HIV-negative volunteers and HIV-infected patients, respectively. χ test indicated a significant relationship between genotype frequencies in both populations (P < 0.001). The minor allele and genotype frequencies obtained in the 2 populations significantly differ and corroborate previous studies, which have reported CYP2B6 516G>T SNP in various other African populations.

Differential Impact of Nevirapine on Artemether-Lumefantrine Pharmacokinetics in Individuals Stratified by CYP2B6 c.516G>T Genotypes

“…Baseline characteristics of sampled participants. The mean (standard deviation) of age (39.8 years [9.7]), body mass index (23.6 kg Ϫ2 [4.9]) and genotype frequencies (%) (GG [38.7] and TT [11.3]) of the cohort of HIV-infected patients previously described (28) were not significantly different from the 30.6 years (11.8); 23.1 kg Ϫ2 (4.6), and GG (42.0) and TT (16.0), respectively, of HIV-negative subjects. However, the sex distribution (number of male [%]) was significantly different between the HIV-infected patients (42 [28.0%]) and HIV-negative subjects (94 [62.7%]) (P Ͻ 0.05).…”

“…In addition, this study investigated effect of homozygosity for CYP2B6 c.516GϾT without consideration for the influence of heterozygosity of this polymorphism. The frequency of GT genotype was 42% (28) in the sampled patients' population, an indication of the fact that majority of the subjects were excluded. Moreover, CYP2B6 c.983TϾC (*18), which is similarly associated with significant reduction in CYP2B6 catalytic activity (48) and also common in African population (49), though with a minor allele frequency of Ͻ10% compared to Ͻ50% of the c.516GϾT, was also not factored into the study due to the limited funds available.…”

“…Study population and design. This was a prospective, open-label, two-arm parallel drug-drug interaction study in HIV-negative volunteers (n ϭ 30) and HIV-infected patients (n ϭ 30) drawn from cohorts of 150 participants each, with previously determined CYP2B6 c.516GϾT genotypes (28). Both the HIV-negative and HIV-infected subjects were without clinical malaria.…”

“…Minor CYP2B6 c.516T allele frequency as high as 50% has been reported in Ghanaian, Mozambican, and Zimbabwean populations compared to almost 20 and 30% in Asian and European populations, respectively (20)(21)(22)(23). Furthermore, frequencies of 23 to 30% for Cape Mixed Ancestry in South African, 31% in Malawian, 29 to 36% in Ugandan, 42% in Tanzanian, and 36 to 40% in Nigerian populations have been reported (23)(24)(25)(26)(27)(28), hence the need to quantify the impact of this SNP on pharmacokinetic drug-drug interactions involving CYP2B6 substrates.…”

Prevalence of Cytochrome P450 2B6 Single Nucleotide Polymorphism in an HIV-Positive Cohort in Jos, Nigeria: Implication for HIV Therapy

“…[ 33 ] A sample size of 316 was utilized based on the formula for sample proportions with a finite correction factor and a hypothesized CYP2B6:516G >T SNP prevalence of 30%+/−5. [ 27 , 34 ]…”