Studies provide support for the role of genetic variation in response to bupropion and nicotine replacement therapy for smoking cessation. Generally, variations in genes within the dopamine and opioid pathways and in nicotine-metabolizing enzymes appear to play a role in the efficacy of nicotine-replacement therapy, while variation in dopamine pathway genes are important for response to bupropion (94). In the one study investigating pharmacological treatment on genetic risk for smoking cessation, genetic variants rs16969968 and rs680244 were used to categorize patients into three haplotypes: (1) low smoking risk allele at rs16969968 and low mRNA expression allele at rs680244, (2) low smoking risk and high mRNA expression, and (3) high smoking risk and high mRNA expression. These haplotypes are located CHRNA5-CHRNA3-CHRNB4 on chromosome 15 and were chosen for their consistent association with measures of smoking heaviness and nicotine dependence in other studies, and potential relation with cessation likelihood. In the smoking cessation trial, haplotype interacted with treatment in affecting success of cessation, in that active treatment was strongly associated with a lower risk of relapse in individuals with haplotype 3 (relative
