Abstract
Human cytochrome P450 (CYP) 2A6 is largely responsible for the catalysis of coumarin and nicotine. In comparison to other human loci, CYP2A6 exhibits a high degree of polymorphism. Some CYP2A6 gene variants have a major effect on phenotypes and presently there are over eighty defined CYP2A6 alleles, which can be divided into either ‘extensive’ or ‘slow’ alleles. Broad individual and inter-ethnic differences in nicotine metabolic rate have been documented. For example, populations of Caucasian and African-descent are commonly cited as extensive metabolizers while Japanese populations are cited as poor metabolizers. Although CYP2A6 has been widely studied by pharmacogeneticists, a consensus regarding the evolutionary mechanisms responsible for generating extensive CYP2A6 diversity is lacking in the literature. The parasite-toxin evolutionary trade-off model explores the possible relationships between nicotine consumption, parasites and CYP2A6 alleles. The Aka are a Central African foraging society that has access to various forms of nicotine, and who are hypothesized in this study to have a higher than expected frequency of slow CYP2A6 alleles in order to help alleviate helminth infection. In order to determine whether or not the Aka can be characterized as a slow or extensive CYP2A6 metabolizing population on average, a genotyping analysis using RFLP and AS-PCR methodologies was performed on 72 blood spots. Alleles assayed include: extensive allele CYP2A6*1B, slow metabolizing alleles CYP2A6*9, CYP2A6*17 and CYP2A6*20, which were found at a frequency of 13.89%, 7.64%, 11.11%, and 0% respectively. Furthermore, the pharmacogenetics and genomics literature was thoroughly reviewed for information interpreting CYPA6 genotyping results, as well as identifying previously CYP2A6 genotyped populations that may be useful for allele frequency comparisons. The genotyping results obtained in this study suggest that the Aka population represent a more extensive metabolizing population, which does not support the study hypothesis. The absence of support for the evolutionary trade-off model and issues that should be addressed for future research are discussed in detail.