Our analyses demonstrate that the majority of variation in conversion of nicotine to cotinine in European Americans following oral administration can be predicted by relatively few CYP2A6 polymorphisms, most with obvious functional mechanisms. The survey of polymorphism presented here does not include non-coding or synonymous variants not previously indicated by the literature as relevant. Nevertheless, the strong genotype/ phenotype correlation reported indicates that most of the polymorphism significantly contributing to variation in these 189 European Americans has been identified, and further important SNPs in this ethnic population are likely to have low minor allele frequencies or small effect sizes. The polymorphism that primarily defines the *1H allele may represent such a variant with an effect size too small to be confirmed by this study.
