WASHINGTON – A review published today in AACC’s Clinical Chemistry journal has identified 10 genes that show promise in predicting how patients will respond to opioid pain medications. Using these genetic markers, healthcare providers could potentially tailor opioid therapy better to curb the skyrocketing rate of deaths from these drugs.
More than 17,500 Americans died in 2015 from prescription opioid overdoses, which is 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. Even in patients with severe pain and a legitimate need for opioids, the dose required to alleviate pain varies widely and unpredictably between individuals. This means that 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. To date, researchers have identified numerous genes that could potentially guide opioid treatment to make it more precise and safe. Despite this, the medical community has only developed treatment guidelines based on one of these genes (CYP2D6) and has not determined which of the other genes should be used in practice.
To identify the genes that could impact patient care the most, a team of researchers led by Ron H.N. van Schaik, PhD, of Erasmus University Medical Center in Rotterdam, the Netherlands, conducted a systematic review of 4,257 studies on opioid genetics. The researchers 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. Using these criteria, van Schaik’s 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 CYP2D6, the most notable of these 10 include SLC22A1, the OPRM1 variant 118A>G, and COMT.
Research shows 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. On the flip side, studies demonstrate that patients with the OPRM1 118A>G variant need higher doses of opioids prescribed but have a lower risk for adverse events. Finally, certain 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.
“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,” said van Schaik. “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.”
Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.aacc.org.
Clinical Chemistry is the leading international journal of clinical laboratory science, providing 2,000 pages per year of peer-reviewed papers that advance the science of the field. With an impact factor of 8.008, Clinical Chemistry covers everything from molecular diagnostics to laboratory management.