Genetic variant might hold key to predicting respiratory depression and personalizing morphine dosage
Better genetic-based predictors of morphine-induced respiratory depression could lead to more personalized pain-relief dosage for children recovering from surgery.
The key was found in μ1 opioid receptor genetic variant A118G, which decreases the binding potential of the μ-receptor in the brain, and therefore increases morphine requirement.
Postoperative respiratory depression is the most serious adverse effect of opioids. Researchers believe genetics accounts for up to 30 percent of the variability in respiratory depression.
The study, published online on Sept. 30, 2014 in The Pharmacogenomics Journal, was led by Senthilkumar Sadhasivam, MD, MPH, and Vidya Chidambaran, MD, both of the Division of Anesthesia, and also involved researchers from the Division of Human Genetics. It was the first clinical study to show significant association of a functionally relevant polymorphism - A118G - of the opioid receptor gene in predicting MIRD susceptibility.
The team analyzed 88 cases of adolescents who had undergone spine fusion for scoliosis, and found that in the first 48 hours after surgery, MIRD in patients with AA genotype was significantly higher. The findings could have wide implications because the variant is present in an estimated 11-17 percent of the Caucasian population.
“This translates to immediate clinical relevance for a large part of the population,” Chidambaran says, “as identifying genotype predicted risk of MIRD will facilitate safer individualized opioid dosing.”
The team also has recently reported additional associations of respiratory depression in children with novel variants of the gene FAAH, published in January 2015, and with ABCB1, published in April 2015.
“These findings show that multiple genes play a role in opioids’ clinical responses,” Sadhasivam says. “As we identify more of these associations, the future of preoperative genetic risk signature stratification and personalizing postoperative pain management in children is promising.”
