Several single-nucleotide polymorphisms (SNP) in the opioid receptor µ-1 (OPRM1) gene have been identified, of which one in particular, SNP rs1799971 (=Asn40Asp, A118G), has been extensively studied with respect to addictive behavior. SNP rs1799971 is a missense variant in nucleotide 118 of the OPRM1 cDNA resulting in an A to G substitution that causes amino acid asparagine (Asn) to be replaced by aspartic acid (Asp) in codon 40 (Bergen et al., 1997). The replacement was originally shown to result in 3-fold increase in β-endorphin binding and receptor activity in vitro (Bond et al., 1998). However, in more recent in vitro studies either the variant has shown more subtle increases in the binding affinity (Befort et al., 2001) or no differences have been observed between the variant and normal receptors (Beyer et al., 2004); some studies have even indicated that the 118G (Asp40) allele would result in decreased mRNA and protein levels (Heinz et al., 2005; Zhang et al., 2005).
