A primary goal of genetic studies of smoking behavior is to identify biological pathways that modulate nicotine consumption and contribute to the development of nicotine dependence. Loci identified as associated with these complex phenotypes include the direct targets of nicotine in the central nervous system, nicotinic receptor subunits[1, 2] and genes involved in the metabolism and clearance of nicotine. Because the psychoactive properties of nicotine closely correlate with its plasma concentration, dependent smokers may titrate nicotine intake and smoking behavior to maintain target nicotine blood levels [3]. For example: dependent smokers given a lower nicotine cigarette than their usual brand inhale more deeply to achieve their typical dose [4]and smokers asked to decrease their cigarette consumption reduce their cigarettes per day (CPD) but increase their intake of nicotine per cigarette [5]. These observations underlie current theories to explain the differences in CPD and craving between fast and slow nicotine metabolizers [6].
