The PENK gene is located on chromosome 8q23. Forty-six coding SNPs have been reported, most of them are rare and some are population-specific. A (CA)n repeat (rs3219515) in the 5′ flanking region was reported to be associated with OD (Comings et al. 1999). Seven SNPs were genotyped in a sample of alcoholic families (COGA) and no association was detected with AD or general illicit drug dependence. Three SNPs (rs2609997 and rs1975285, in the 5′ flanking region, and the intronic rs1437277) provided evidence of association with opioid dependence in a small subsample (Xuei et al. 2007). In another study of a different (CA)n repeat (rs3138832) in the 3′ flanking region, a significant association of a specific allele (CA)79 (based on PCR product described in Weber and May 1990), with heroin abuse was reported in a European sample. This allele was also associated with higher striatal PENK mRNA expression in the fetal postmortem human brain, but not adult brain (Nikoshkov et al. 2008). In another study of AD in two European cohorts, four SNPs were analyzed and two SNPs (rs12545109 and rs2576581) showed association in the German cohort but not in the Swedish cohort (Racz et al. 2008).
