The MOR binds endogenous beta-endorphin, the release of which increases upon nicotine administration; activation of the MOR results in dopamine release within the nucleus accumbens, possibly through inhibition of GABAergic inhibition of dopaminergic neurotransmission (18). The potential involvement of the OPRM1 gene in smoking related phenotypes is supported by multiple analyses. A novel linkage analysis of existing data and bioinformatic analyses of extant literature reported positive correlations between linkage analyses of nicotine dependence, microarray/candidate gene studies, and biological pathway analyses (19). Analysis of seven OPRM1 SNPs identified several haplotypes significantly associated with smoking initiation and two haplotypes marginally associated with nicotine dependence (20). The OPRM1 non-synonymous (Asn40Asp) SNP (rs1799971) has been significantly associated with long-term smoking cessation in interaction with gender (18).
