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The Pharmacogenetics of Nicotine Dependence and Smoking Cessation Therapies

Martin M Zdanowicz and Patti W Adams

Tobacco-related diseases place a tremendous burden on health-care systems world-wide. Overall mortality for smokers is nearly three-fold higher than for similar non-smokers. This increased mortality results from higher rates of cancers, vascular disease or respiratory disease. Great strides have been made in recent years with regards to understanding the neurophysiologic pathways of nicotine addiction. While a number of pharmacologic interventions have been developed to aid patients in smoking cessation, overall success rates for long-term smoking abstinence remain disappointingly low.
A growing body of evidence suggests that a number of genetic factors might influence both the severity of an individual’s nicotine addiction as well as the potential efficacy of various treatment modalities they might employ. The neurophysiology of nicotine addiction will be discussed along with genetic variants that can impact both nicotine pharmacodynamics and pharmacokinetics. The role that genetic variation plays in altering the efficacy of various smoking-cessation therapies will also be reviewed along with the potential therapeutic and economic benefits of utilizing genetic testing to optimize such drug therapies.