Allelic variants of CYP2B6 gene expression and its implication on the pathogenesis of malaria among a cohort of outpatients in North-Central Nigeria

Abstract

Abstract Background Human cytochrome P450 2B6 (CYP2B6) is fortified with the biotransformation of the antimalarial, artemisinin combination therapy (ACT). Owing to emerging reports of Plasmodium species resistance to ACT in other climes, CYP2B6*6 genotype significantly alters ACT metabolism. In North-Central Nigeria, the distribution of the CYP2B6*6 variant is poorly documented. This study investigated the distribution of CYP2B6 c.516G>T variants and its relationship with certain malaria pathogenesis among a cohort of clinical-malaria outpatients in Ilorin, Nigeria. Methods A total of 50 symptomatic P. falciparum malaria-positive samples were genotyped for CYP2B6 c.516G>T using restriction fragment length polymorphism and a specific haplotype population was established. The allele frequencies and genotype distributions were analyzed. Haplotypes were clustered using Ward’s method. Correlations determined include defective CYP2B6 versus parasitemia densities and thrombocytopenia, respectively. Results Forty-five samples show genotypic ratios and nine CYP2B6 genetic single nucleotide polymorphisms were identified. The following haplotypes (64C>T = *1/*2, 785A>G = *1/*4, and 1459C>T = *1/*5) occurred and *2, *3, and *18 alleles harbor 64C>T, 777C>A, −82T>C, and 499C>G. The codon 64CT, 516GT, and 785AG; −82TC and 777CA; and 499CG, 516GT, and 785AG were identified as *2/*6 heterozygotes. Samples with 516GT and 785GG genotypes occurred with *4/*6 heterozygotes. Mutant trait alleles recorded high parasitemia 72 h post-ACT regimen. Only individuals with CYP2B6*6 alleles had severe malaria and thrombocytopenia. Conclusion This report contributes to the growing knowledge of CYP2B6*6 genotype frequency and its relationship with malaria pathogenesis among a Nigerian population.