Our study also had several limitations. First, due to the small number of smokers with the Met/Met genotype, this group was combined with the Met/Val group. As a result, we could not test for the differences between the Met/Met and Met/Val groups. Similarly, due to small sample sizes of the race and sex subgroups, we could not conduct detailed analysis to explain race and sex interactions with the COMT Val158Met polymorphism. Second, the smokers were tested once following overnight abstinence from smoking. For optimum assessment of withdrawal or cognitive performance, multiple days of abstinence from smoking may be needed. Third, the IV nicotine responses may not be generalizable to cigarette smoking, given that tobacco addiction includes both nicotinic and non-nicotinic components (65). Fourth, we did not assess smokers during a smoking as usual condition, which would have allowed further delineation of the influence of COMT Val158Met polymorphism on the study outcomes. Lastly, we did not correct for multiple testing due to exploratory and hypothesis-generating nature of the study. Thus, the results should be interpreted cautiously, although we fell they warrant replication in larger studies.
