Smokers who are partially or totally deficient in this enzyme owing to carriage of the variant allele of some CYP2A6 polymorphisms are ‘poor’ (or ‘slow’) nicotine metabolizers; as such, they are theoretically expected to have a reduced need for cigarette consumption compared with the wild-type genotype [25], [26] However, it is also possible that prolonged high levels of brain nicotine owing to reduced metabolization might increase the risk for nicotine dependence, leading to a certain ‘nicotine tolerance’ phenomenon [27], [28]. The gene discussed is CYP2A6; the disease is nicotine dependence.