availability of α4β2 nAChRs compensates for damaged protein function. Alternatively, an increase in stability of the mutated α4 protein could increase baseline nAChR function, providing protection against further increases by the nicotine in tobacco. The results from this imaging study are preliminary, and these hypotheses remain to be tested. For smokers carrying nonsynonymous rare variants, Chronic exposure to nicotine up-regulates α4β2 nAChRs (43), and this may mask the effect of rare variants. It is hard to generalize based on these findings however, because it is plausible that each specific variant could have a unique effect on function. These findings should therefore be viewed as illustrative of possible effects rather than predictive of all.
