Given the recognition that the opioidergic system may underlie some of the reinforcing effects of alcohol, there has been recent scientific interest in the genes encoding for endogenous opioid receptors, with a particular focus on the mu-opioid receptor gene (OPRM1). One of the most widely studied polymorphisms of the OPRM1 gene is the +118A/G SNP located in the +118 position in exon 1, which codes for the AsnAsp40 substitution (rs1799971). Molecular studies of this polymorphism initially suggested that the A to G substitution affects receptor activity for endogenous ligand β-endorphin leading to a gain in function, such that the Asp40 variant (i.e., G allele) was though to bind β-endorphin three times stronger than the Asn40 (i.e., A) allele (Bond et al., 1998). However, a more recent study of the functional significance of this SNP suggested that the Asp allele has deleterious effects on both mRNA and protein yield, leading to a loss of function, rather than a gain (Zhang et al., 2005).
