An extensive search for functional OPRM1 polymorphisms has identified a few alternative loci with a relatively high allelic frequency, which can mediate a significant degree of the variable clinical effects observed in a population (reviewed in 16). These alternative loci were found in the promoter, coding and intron regions of the gene, which are associated with the diverse pharmacological and physiological effects mediated by OPRM1 stimulation. However, among SNPs with a relatively high reported allelic frequency, which can mediate a significant degree of the variable clinical effects observed in a population, only the A118G OPRM1 SNP (Asp40Asn) has been repeatedly shown to have functional consequences. This missense SNP changes the N-terminal region amino acid asparagine to aspartic acid, which decreases the number of sites for N-linked glycosylation of the MOR receptor from five to four, providing strong rational for association studies. Several studies have demonstrated a relationship between the frequencies of the A118G OPRM1 genomic polymorphisms and OPRM1-dependent phenotypes, including responses to opiates (22–25) and variations in pressure pain thresholds (26). However, only a small percentage of the variability of
