Genetic Influences on Opioid Use in Low Back Pain: OPRM1 rs1799971

Abstract

Purpose: The OPRM1 rs1799971 single nucleotide polymorphism (SNP) has been studied for its influence on drug abuse and opioid use. Opioids have a questionable long-term risk-benefit profile in chronic low back pain, and a genetic predisposition to taking higher doses could place a patient at higher risk of complications related to opioid use. Studies have demonstrated higher dosages of self-administered opioids in an acute post-surgical setting in subjects with the rs1799971 AG polymorphism. We hypothesize that subjects with the rs1799971 AG polymorphism will use higher doses of opioids than subjects with other rs1799971 polymorphisms in the setting of chronic low back pain. Methods: This study was conducted using data from the PRECISION Pain Research Registry at UNTHSC. A saliva sample from each subject was obtained to determine genotypes, including the OPRM1 rs1799971 SNP. Additionally, numerical ratings of low back pain intensity and opioid use in morphine milligram equivalents (MMEs) were measured. The MMEs were computed in accord with CDC guidelines, which further indicate that opioid doses greater than 50 MMEs per day double the risk of opioid complications as compared with doses under 20 MMEs per day. We analyzed pain intensity, daily MMEs, and the proportion of subjects taking doses in excess of 50 MMEs per day based on allele status at SNP rs1799971. Results: Of 351 subjects with subacute or chronic low back pain, 279 were AA and 72 were AG. There was no significant difference in MMEs between rs1799971 AA subjects (x̅=5.90, SD=17.03) and AG subjects (x̅=9.53, SD=22.85). AG subjects had statistically significant lower pain intensity (x̅=5.2777 SD=1.74) compared to AA subjects (x̅=5.985, SD=1.9489 Mann-Whitney U=7897.5 p=0.005). rs1799971 AG subjects were more likely to be taking opioid doses greater than 50 MMEs per day than AA subjects (OR=3.40 95% CI:1.01-11.46 p=0.04). Five and 6 subjects with AG and AA, respectively, were taking doses greater than 50 MMEs per day (OR, 3.40; 95% CI, 1.01-11.46; Fishers exact p=0.11) Conclusion: There was no significant difference in mean MMEs among rs1799971 AG and AA subjects. However, AG subjects were marginally more likely than AA subjects to be taking doses greater than 50 MMEs per day. This SNP could potentially place rs1799971 AG patients at higher risk of complications relating to higher opioid doses, indicating a less favorable risk-benefit profile for long-term opioid therapy.