A brief review of the genetics and pharmacogenetics of opioid use disorders.

Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes (KCNC1 and KCNG2) and in a glutamate receptor auxiliary protein (CNIH3). Additionally, a variant at the µ-opioid receptor gene (OPRM1), which regulates OPRM1 expression appears promising. In pharmacogenetics of opioid addictions, methadone dose may be regulated by variants in cytochrome P450 2B6 (CYP2B6), a methadone-metabolizing enzyme, and by a locus 300 kb 5' to OPRM1. A δ-opioid-receptor gene single-nucleotide polymorphism may predict treatment response to methadone versus buprenorphine. To achieve better progress, larger sample sizes are needed for GWAS research, including controls with chronic opioid exposure, but no addiction. Large clinical trials comparing effective pharmacotherapies for opioid addiction (naltrexone, methadone, and buprenorphine) are needed for pharmacogenetic progress.