The 81st Annual Meeting of the American Association of Physical Anthropologists (2012)


The highly polymorphic human cytochrome P450 (CYP) 2A6 gene: examining diversity and nicotine metabolism in a central African foraging population

HAYLEY A. MANN1, BRIAN M. KEMP2,3, ROGER J. SULLIVAN1 and EDWARD H. HAGEN4.

1Anthropology, California State University, Sacramento, 2Anthropology, Washington State University, Pullman, 3School of Biological Sciences, Washington State University, Pullman, 4Anthropology, Washington State University, Vancouver

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Human cytochrome P450 (CYP) 2A6 is largely responsible for the catalysis of coumarin and nicotine. In comparison to other human loci, CYP subfamily 2A6 exhibits a high degree of polymorphism. Some CYP2A6 gene variants have a major effect on phenotypes. Presently, there are over eighty defined CYP2A6 alleles that fall into three metabolic categories: extensive, poor and null. Broad individual and inter-ethnic difference in nicotine metabolic rate have been documented. For example, Caucasian and African-descent are commonly cited as extensive metabolizers while Japanese are cited as poor metabolizers. Although CYP2A6 has been widely studied, a consensus regarding the evolutionary mechanisms responsible for generating extensive CYP2A6 diversity is lacking in the literature. More CYP2A6 genotyping data from diverse populations is necessary for formulating more precise evolutionary explanations and to date, only one African population has been previously studied. We have conducted a study of CYP2A6 variation and its relationship to smoking behavior in a Central African Aka population—a foraging society that has access to various forms of nicotine. The presence of specific CYP2A6 alleles in blood spot samples were assayed using RFLP, allele-specific PCR and direct sequencing. Alleles tested include: extensive allele CYP2A6*1B, poor metabolizing allele CYP2A6*9 and poor metabolizing African allele CYP2A6*17. These alleles were detected in frequencies similar to those described for African and African-descent populations. We discuss several explanatory evolutionary models of extant variation in the African and non-African CYP2A6 genotype.

This investigation was supported in part by funds provided for medical and biological research by the State of Washington Initiative Measure No. 171.

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