Genetic influences on relapse have been studied most extensively in the context of pharmacogenetics, with the bulk of studies focusing on nicotine dependence (for recent reviews see [83,84]). Several candidate polymorphisms have been examined in response to smoking cessation treatments, especially nicotine replacement therapy (NRT) and bupropion [84]. The catechol-O-methyltransferase (COMT) Val158Met polymorphism, established as predicting variability in prefrontal dopamine levels, has been evaluated in relation to smoking cessation in several studies. Independent trials of NRT have found cessation rates to differ based on COMT genotype [85-87]. A polymorphism in the nicotinic acetylcholine ß2 receptor gene (CHRNB2) has been associated with length of abstinence and withdrawal symptoms during bupropion treatment [88] and with relapse rates and ability to quit on the target day during NRT [89]. One bupropion trial found that DRD2 variations predicted withdrawal symptoms, medication response and time to relapse [90]. In a study of the mu-opioid receptor (OPRM1) Asn40/Asp40 variant during NRT, those with the Asp40 variant had higher rates of abstinence and reduced negative affect compared to Asn40 individuals [91]. Additionally, post-hoc analyses indicated that Asp40 carriers were more likely to regain abstinence following a lapse, suggesting a possible role of the genotype in predicting prolapse.
