It will be important to understand the mechanistic basis of the association of genetic variants with smoking cessation. Nicotinic receptors are involved in many neuronal functions, including differentiation and synaptic plasticity, which are the basis for learning and memory. Response inhibition, attention, and working memory are influenced directly by nAChRs or through nAChR interactions with other neurotransmitter systems (Rezvani and Levin 2001). The cognitive signs of nicotine withdrawal are believed to be an important factor in failed cessation attempts and continued use (Koob et al. 1993; Markou et al. 1998; Patterson et al. 2010). The nAChR CHRNA4 SNP rs1044396 contributes to individual differences in visuospatial attention (Greenwood et al. 2005) and another study showed a strong association of rs6090384 with severe inattention (Todd et al. 2003). Recent tobacco use improved cognitive flexibility in European American smokers with variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster, implying that nicotine can enhance various aspects of cognitive processing by activation of nicotinic receptors and may modulate the effect of genetic factors on cognitive flexibility (Marchant et al. 2008; Zhang et al. 2010)
