부산대학교 도서관

Malaria remains a disease of major public health concern globally, with endemicity more pronounced in the sub-Saharan Africa while children below the age of five alongside pregnant women are the most affected groups. The artemisinin combination therapy (ACT) is the recommended first line treatment for Plasmodium falciparummalaria in Nigeria. However, Single nucleotide polymorphisms of the cytochrome P450 2B6 gene (known for the primary induction of artemisinin) can affect the enzyme function as it either enhances, decreases, or abolishes its enzymatic activities depending on the drug substrates. This study investigated the frequency of commonly observed CYP2B6 variants (516G > T {rs3745274}, 785A > G{rs2279343}, 64C > T {rs2279345}) and the association with malaria in a Yoruba population of Nigeria. Genotyping of CYP2B6 genetic polymorphisms was carried out among 200 children using PCR-RFLP protocol. Statistical package for social sciences (SPSS) was used in analyzing demographic and clinical data. Genotypic and Allelic frequencies were calculated, conformity with Hardy-Weinberg equilibrium and associations were tested for under three different genetic models using PLINK v1.90 and Haploview 4.2. We observed a minor allelic frequency (MAF) of 0.12, 0.375, 0.423 for 785A > G, 64C > T and 516G > T allelic variants respectively. The Three SNPs were not in linkage disequilibrium, the variants 785A > G and 516G > T were in conformity with Hardy-Weinberg equilibrium. The genotype distributions of 785A > G and 64C > T differed significantly across all malaria groups. Further analysis showed a statistically significant association of 785 A > G with malaria. The 785A > G variant under the dominant and additive genetic models reduced the risk of developing uncomplicated malaria (95% CI = 0.15–0.81, OR = 0.35, p = 0.0142) and severe malaria (95% CI = 0.20–0.97, OR = 0.44, p = 0.0439) from asymptomatic malaria. This finding indicates that the cytochrome p450 gene variant, 785A > G may confer protection against malaria development in addition to its drug metabolism functions. Further large-scale studies on CYP2B6 variants are recommended to explore the impact in malaria development or susceptibility.