Comprehensive mu-opioid-receptor genotyping by pyrosequencing.

Abstract

The human μ-opioid receptor, encoded by the OPRM1 gene (1)(2), is the major site for the analgesic action of opioids. The OPRM1 gene is therefore a first-line candidate for evaluating the role of mutations on the clinical effects of opioids. The mutant allele of the 118A>G single-nucleotide polymorphism (SNP) in the OPRM1 gene, which codes for an Asn40Asp μ-opioid receptor, has been associated with decreased opioid activity in carriers of the 118G allele. Morphine 6-glucuronide (M6G) and morphine have lower potencies for pupil constriction in carriers of the mutation, who also vomit less often after treatment with M6G than noncarriers (3). Carriers of the 118G allele need more alfentanil for postoperative analgesia but have less pain relief than noncarriers (4). The 118G allele has also been associated with a greater cortisol response to opioid receptor blockade with naloxone (5). Regarding opioid addiction, the mutant allele of the 17C>T SNP was found more frequently in drug addicts than in nonaddicts (6)(7). An association between the mutant alleles of the 118A>G (exon 1) and 691C>G (intron 2) SNPs and opioid dependence was reported for Chinese heroin addicts, although this was based on a small study group (8). The frequency of the mutated 118G allele was higher in Indian heroin addicts than in controls (9). Addicted individuals carrying both the mutated 118G allele and the mutated 31A allele in intron 2 consumed higher doses of heroin than individuals who did not carry these mutations (10). The simultaneous presence of the mutated alleles for SNPs −1793T>A, −1699-(−1698)insT, −1320A>G, −111C>T, and 17C>T is associated with substance dependence (11). In European Americans, allele −2044A and haplotypes that include −2044A were found to be associated with susceptibility for substance dependence (12). To promote further investigation of an association of OPRM1 mutations …