Pharmacogenetics and smoking cessation with nicotine replacement therapy

Nicotine replacement therapies (NRTs), including transdermal patch, gum, lozenge, nasal spray and inhaler, are widely used for the treatment of tobacco dependence; however, only one-quarter to one-third of smokers who utilise NRTs to quit smoking are able to maintain long-term abstinence from tobacco use. Pharmacogenetic studies of NRT may be useful to identify subgroups of smokers who respond more favourably to specific NRTs, and to determine the optimal dose and duration of NRT. To date, pharmacogenetic studies have examined genes coding for nicotine metabolising enzymes, as well as proteins in neurotransmitter pathways that mediate the effects of nicotine. Initial findings suggest that polymorphisms in nicotine metabolising enzymes, and selected genes in the dopaminergic and opioidergic pathways, may have predictive validity for NRT response; however, independent replication is necessary before translation to clinical practice. Largerscale investigations that incorporate pathway-based or genome-wide analysis, as well as intermediate measures of nicotine dependence (i.e. 'endophenotypes'), may be necessary to capture the complexity of pharmacogenetic effects.