Pharmacogenomics of Tobacco Addiction
Johnstone E., Munafò M., Neville M., Griffiths S., Murphy M., Walton R.
The precise mechanism of nicotine addiction and the influence of genetics on smoking behavior are beginning to be elucidated. A major challenge for the new science of pharmacogenomics is to utilize recent discoveries in genetics to improve existing smoking cessation therapies. Traditional candidate gene studies show that genetic polymorphisms affecting nicotine metabolism and dopaminergic transmission increase the susceptibility to tobacco dependence. Chromosomal regions in which other relevant genes may be located have recently been identified by genome scans. Combining these techniques may open the door to largescale rationally designed studies to identify new genes that are important in the development of nicotine dependence. Animal models have also been used to unravel genetic influences on the behavioral effects of nicotine and highlight in particular the important role that the acetylcholine receptor plays in nicotine action. This chapter reviews these various approaches to elucidating the genetic basis of nicotine dependence. We explore the potential benefits of classifying smokers according to the molecular etiology of their habit in order to plan individually targeted cessation strategies.