Prior pharmacogenetic studies have focused on the OPRM1 gene, which codes for mu-opioid receptors, for which naltrexone has highest binding affinity (Goldman et al., 2005, Oslin et al., 2003). One of the most widely studied polymorphisms of the OPRM1 gene is the A118G single nucleotide polymorphism (SNP) (rs1799971). Studies of the functional significance of this variant have produced mixed results with some reports suggesting that the 118G variant binds more strongly to β-endorphin than the major allele when expressed in Xenopus oocytes (Bond et al., 1998) while others have not replicated this result for β-endorphin or found differential binding of morphine when assayed in human embryonic kidney cells (Beyer et al., 2004). Additionally, the 118G variant appears to decrease OPRM1 mRNA and protein yield suggesting that this SNP may function more as a loss of function effect (Zhang et al., 2005).
