US 12,146,193 B2
Methods and compositions relating to OPRM1 DNA methylation for personalized pain management
Vidya Chidambaran, Cincinnati, OH (US); Senthilkumar Sadhasivam, Mason, OH (US); Hong Ji, Cincinnati, OH (US); and Lisa Martin, West Chester, OH (US)
Assigned to Children's Hospital Medical Center, Cincinnati, OH (US)
Filed by Children's Hospital Medical Center, Cincinnati, OH (US)
Filed on Mar. 7, 2023, as Appl. No. 18/179,607.
Application 18/179,607 is a continuation of application No. 16/478,706, granted, now 11,618,924, previously published as PCT/US2018/014405, filed on Jan. 19, 2018.
Claims priority of provisional application 62/448,540, filed on Jan. 20, 2017.
Prior Publication US 2023/0265518 A1, Aug. 24, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/6883 (2018.01)
CPC C12Q 1/6883 (2013.01) [C12Q 2600/106 (2013.01); C12Q 2600/154 (2013.01)] 21 Claims
 
1. A method for mitigating an atypical opioid response manifesting as perioperative pain in a human subject in need thereof, the method comprising
assaying, in vitro, a biological sample from a subject to determine a methylation status of at least one CpG site in the human mu-1 opioid receptor gene (OPRM1),
wherein the at least one CpG site in OPRM1 is selected from the group consisting of CpG sites 1, 3, 4, 9, 11, 13, 17, and 22 as defined in Table 4,
identifying the subject in need thereof as one who is susceptible to the atypical opioid response where the susceptible subject has a methylation status of “methylated” at the at least one CpG site, and
administering to the susceptible subject identified as susceptible to the atypical opioid response a demethylating agent, an inhibitor of the repressor element-1 silencing transcription factor (REST) and/or a regimen of multimodal analgesia for perioperative pain management, thereby mitigating the atypical opioid response in the susceptible subject.