A recent family-based study in European Americans demonstrated that variations in OPRK1, the gene encoding the KOR, and in PDYN, which encodes its dynorphin ligand, were associated with alcohol dependence (17). The associated SNPs in OPRK1 were in intron 2 of the gene; two coding SNPs were not associated (17). The association of OPRK1 with alcoholism was confirmed by a second study, reporting that a haplotype of OPRK1 was associated with alcohol dependence (18), although individual SNPs were not; it should be noted that Zhang et al. (18) did not test any SNPs in intron 2, the region where association had earlier been reported. An earlier study of three coding SNPs in Taiwanese Han subjects found no association between OPRK1 and alcohol dependence (19). The finding that non-coding SNPs, but not coding SNPs, were associated with alcohol dependence suggests that the association is with regulatory variation in the gene. Non-coding OPRK1 variations have also been associated with opioid addiction (20), as was the coding SNP G36T (21). The association of variants in PDYN with alcohol dependence was also replicated (22).
