tolerance, such that those with a greater daily intake of nicotine are more tolerant and therefore experience less nausea in response to a nicotinic partial agonist such as varenicline. Alternatively, incidence of nausea may be elevated in subjects with greater risk for nicotine dependence because their nicotine intake is greater before quitting, therefore exacerbating the symptoms of withdrawal on quitting. SNPs associated with nausea are also linked to SNPs associated with the expression of CHRNA5, suggesting another mechanistic link between nicotine dependence and nausea on quitting. For subjects treated with varenicline, CHRNG, which encodes the nAChRγ subunit, is also associated with nausea. The importance of this locus for nausea in the varenicline-treated subjects is not clear, although recent studies have identified associations with this region, which also includes the CHRND gene, and nicotine dependence (Saccone et al, 2009), suggesting that the association with nausea may also be driven by nicotine dependence.
