Several genetic association studies have tested the relationship between the Asn40Asp SNP and substance use disorders, particularly alcoholism and opioid dependence. The results, however, are inconsistent, and while some investigations have found support for the association between this SNP, as well as other intronic OPRM1 SNPs (Kranzler et al., 1998), and alcohol or opioid dependence (Bart et al., 2005; Schinka et al., 2002; Tan et al., 2003; Town et al., 1999), other studies have failed to report an association (Bergen et al., 1997; Crowley et al., 2003; Franke et al., 2001; Gelernter et al., 1999; Shi et al., 2002), including haplotype-based analyses (Luo et al., 2003). A family-based association study by Xuei and colleagues (2007) examined multiple SNPs of the mu (OPRM1) and delta opioid receptor (OPRD1) genes, as well as genetic polymorphisms in the genes encoding for their endogenous ligands (POMC and PENK). Results did not support associations between these genes and alcohol dependence (Xuei et al., 2007). However, other family-based association analyses showed an effect of genes encoding the kappaopioid receptor (OPRK1) and its ligand (PDYN) with regard to alcohol dependence liability (Xuei et al., 2006).
