Nicotine exerts its pharmacologic effects by acting on nicotinic cholinergic receptors in the brain. In Caucasians, multiple independent SNPs (single-nucleotide polymorphisms) in the CHRNA5-A3-B4 gene cluster, which encodes for the α5, α3 and β4 subunits of the nicotinic acetylcholine receptor (nAChR), have been associated with smoking quantity (7-13) and smoking cessation outcomes (14-18). These loci included rs16969968 and correlated SNPs (sometimes referred as ‘Bin A’ or ‘Locus 1′), rs588765 and correlated SNPs (sometimes referred as ‘Bin B’ or ‘Locus 3′), and rs578776 and correlated SNPs (sometimes referred as ‘Bin C’ or ‘Locus 2′) (11, 19). However, it is not clear whether the influence of CHRNA5-A3-B4 gene variants on smoking cessation is a general effect on smoking cessation (i.e. would alter cessation in placebo treatment), is independent of the specific type of pharmacological treatment (ie would alters all active treatments) or alters cessation for specific pharmacological treatments (i.e nicotine patch). For example, one study suggested that the association between CHRNA5-A3-B4 variants (rs16969968 [Bin A] and rs680244 [Bin B]) and smoking cessation is primarily observed among smokers treated with placebo, and was
