Opioid-Related Deaths Possibly Prevented By Gene Testing

More than 17,500 Americans died in 2015 from prescription opioid overdoses, which are more than quadruple the amount of people who died from this cause in 1999, but it is not just abuse of these medications that can lead to overdoses.

Clinicians must essentially use a trial and error strategy to determine the correct type of opioid and dosage that will help a patient. This approach puts some patients at increased risk of life-threatening side effects such as respiratory depression, while leaving other patients undertreated and in pain.

Scientists at the Erasmus University Medical Center (Rotterdam, the Netherlands) conducted a systematic review of 4,257 studies on opioid genetics. They assessed the utility of each gene studied based on whether a) several independent studies confirmed the gene’s effect on patient opioid response and b) the gene’s frequency in the white population was high enough for use in screening tests. The team pinpointed 10 genes that show the highest potential of refining the way opioids are prescribed and that healthcare providers should focus on implementing clinically. In addition to the already well-known cytochrome P450 family 2 subfamily D member 6 (CYP2D6), the most notable of these 10 include Solute Carrier Family 22 Member 1 (SLC22A1), the opioid receptor kappa 1 (OPRM1) variant 118A>G, and Catechol-O-methyltransferase (COMT).

The team found that the presence of two inactive SLC22A1 genes leads to high blood concentrations of tramadol’s active metabolite and, in children, to significantly lower clearance of morphine. This means that patients with these mutations might be at increased risk of overdosing from tramadol and morphine, particularly if they also have certain CYP2D6 mutations. COMT mutations are associated with both lower opioid requirements and fewer side effects, while still other COMT mutations have been linked with the highest pain scores and opioid consumption in patients who have undergone surgery. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly.

Ron H.N. van Schaik, PhD, a professor and European specialist in laboratory medicine, said, “The most solid evidence of a clinically relevant pharmacogenetics effect on the analgesic treatment with opioids is available for genetic variation in CYP2D6, COMT, SLC22A1, and the genetic variant OPRM1 118A>G. As clinical guidelines for codeine and CYP2D6 genotyping have been formulated and CYP2D6 genotyping has been successfully implemented in pediatric clinical practice. The application of pharmacogenetics in the management of pain with opioids certainly has the potential to improve therapy.” The study was published in the June 2017 issue of the journal Clinical Chemistry.

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Erasmus University Medical Center