Your genes and your opioids: Pain relief or addiction? Or both?

Are there currently potential candidate genes that would allow to test for such a predisposition to addiction? Research shows that indeed there are such candidates. Thus, a common variant of theµ-opioid receptor gene alters opioid sensitivity and has been linked to less pain relief and more susceptibility to addiction. Patients with this particular gene variant are more likely to experience higher levels of pain at standard opioid doses and therefore require higher concentrations for pain relief; high opioid dosages makes addiction more likely in general. This gene variant is named A118G OPRM1 for the nucleotide switch (adenine to guanine) at position 118 in the opioid receptor µ-1 gene. This gene variant leads to the synthesis of an altered µ opioid receptor protein, which loses an important amino acid (asparagine) for sugar attachment and gains an aspartic acid. This loss of the asparagine and the attached sugar chain alters the shape of the protein and likely alters its function.

There are other gene candidates linked to opioid addiction. One family of genes that has been analyzed is involved in dopamine regulation. A dopamine 2 receptor allele (called rs1800497) was compared in drug users and controls and has been linked to high heroin use and unsuccessful methadone use. Another dopamine-related gene, dopamine 4 receptor, contains a region with a variable number of nucleotide repeats; for , the gene may have a stretch with 3 repeats (ATATAT) or a stretch with 6 repeats (ATATATATATAT). People with the higher numbers of repeats (5 to 7 copies of the repeat) have the desire to try new things (called novelty-seeking behavior). Heroin users often have the dopamine 4 receptor gene variants with a higher numbers of repeats.

Besides the A118G OPRM1 gene, other opioid receptor alleles have also been found to be associated with addiction, for example the C17T OPRM1 gene variant. The combination of the G80T opioid receptor δ 1 (OPRD1) gene allele with the normal allele (G80G), as well as the C921T OPRD1 gene, was found to be more prevalent in heroin users than in controls. OPRK1 is considered a candidate gene because it is involved with the stress response and counteracts the euphoria induced through OPRM1. One allele of this gene (rs1051660) was found more frequently in heroin users.

Neurotrophins, or regulatory proteins that modulate neuronal growth, survival, and differentiation, are also candidate genes linked to addiction. Some variants of the neurexin gene are associated with increased impulsive reactions and behaviors that often lead to more drug use.