As described earlier, there are multiple CYP2B6 variants that are reported to have functional effects, and two of these have been examined for associations with smoking cessation in bupropion pharmacogenetic trials. Although CYP2B6 appears to have little influence in peripheral nicotine metabolism, expression of this enzyme in the brain suggest potential influences on nicotine-addiction phenotypes, such as ability to quit smoking (Miksys et al., 2003). Of particular relevance to bupropion, the CYP2B6 enzyme is the primary enzyme involved in the metabolism of bupropion to its metabolites, hydroxybupropion, erthrohydrobupropion, and threohydrobupropion (Faucette et al., 2000); however, the parent compound and metabolites are biologically active, and thus, rates of bupropion metabolism may not affect outcome. The CYP2B6*5 (C1459T) variant has been associated with reduced protein expression and bupropion metabolism (Hesse et al., 2004; Lang et al., 2001). The CYP2B6*6 (G516T and A785G) variant has also been associated with decreased bupropion metabolism (Hesse et al., 2004; Loboz et al., 2006). These variants in the CYP2B6 gene are in high linkage disequilibrium (Johnstone et al., 2006), and many studies have focused on individual SNPs rather than alleles (e.g., C1459T is also found in *7).
