Challenges and cautions with small and retrospective postoperative pain genome-wide association studies with TAOK3

Modulatory effects of TAOK3 variants on morphine requirement in acute postoperative pain: An early genome wide association study contribution to the field of pediatric pain

“…The 4.0% of discovery cohort children who had no oral opioids received 17.9 lg/kg less morphine in recovery and 12.9 lg/kg less total morphine. That is, the claimed effect direction [13] is opposite that of our findings. Further, the absolute value of the purported ''effect size'' (12.9 lg/kg) is clearly less than that for the top minor alleles at TAOK3 (17.6 lg/kg/minor allele, hence 35.2 lg/kg for homozygotes).…”

“…Oxycodone would likely reduce morphine requirement were morphine titrated for pain control beyond the postanesthesia care unit period. Dr. Sadhasivam et al [13] make erroneous assertions regarding causality and ''oxycodone effect size.'' The 4.0% of discovery cohort children who had no oral opioids received 17.9 lg/kg less morphine in recovery and 12.9 lg/kg less total morphine.…”

“…Consistent with this are dose statistics for n = 3899 subjects who had tonsillectomy and adenoidectomy with intraoperative morphine-average 91.9 lg/kg; SD 29.4 lg/kg; range 9.6 to 283.0 lg/kg compared with the final discovery cohort with an average of 88.2 lg/kg; SD 26.9 lg/kg; and range 24.8 to 272.7 lg/kg. Any of the complications or unanticipated hospital admissions mentioned [13] would have occurred after blood sample donation for genotyping and would not have resulted in bias.…”

The Diverse Roles of TAO Kinases in Health and Diseases

“…Interestingly, TAOK2 was found to be recruited to the internalization vacuole containing intracellular bacteria in Listeria monocytogenes infected cells and involved in regulation of vacuolar rupture and cytoplasmic access of these bacteria [ 73 ]. Genetic variations in the TAOK3 locus rs795484 were reported to be associated with increased morphine requirement in children of European Caucasian ancestry and with increased acute postoperative pain in both European Caucasian and African American subjects [ 74 , 75 ], although the underlying mechanism is unknown and requires further determination [ 76 ]. It has been proposed that TAOK3 may act as a pharmacogene that affects the response to analgesic treatment [ 77 ].…”