Association of ABCB1 (rs1045642) single nucleotide polymorphism and drug metabolism reserve index (DMRI) with pain intensity among adults with chronic low back pain

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2019-03-05

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Licciardone, John C.
Phillips, Nicole R.

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Purpose Low back pain is the leading cause of disability in the United States. It is often associated with long term opioid use, which may lead to opioid misuse and serious adverse events. Current clinical guidelines caution that opioids may provide only a small to moderate therapeutic effect, despite these potential risks. This study explores the use of pharmacogenetics in patients with chronic low back pain who are managed with opioids by investigating nucleotide variants in ABCB1,a gene implicated in drug bioavailability. Additionally, a three gene model using CYP2D6, CYP2C9, and CYP2C19, will be used to determine opioid drug metabolism on a quantitative scale. We aim to identify pharmacogenetics variants that may lead to safer and more effective treatment of chronic low back pain in patients being managed with opioids. Methods This study included 102 patients with low back pain within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION). All patients in the study reported using opioids for their low back pain. DNA genotyping of biological samples from all patients was conducted on Illumnina iScan Global Screening Array. A common SNP locus (C3435T, rs1045642) in ABCB1was genotyped. Additionally, SNPs for CYP2D6, CYP2C9, and CYP2C19 were used to construct the drug metabolism reserve index (DMRI) for each patient, which was then stratified as Sub-functional (DMRI 6). Outcome measures included a numerical rating scale for low back pain intensity, the Roland-Morris Disability Questionnaire, and the PROMIS-SPADE cluster for quality of life. The Mann-Whitney test was used for statistical analysis in SPSS. Results Patients with the T allele at rs1045642, which inhibits ABCB1 protein function and increases drug bioavailability, reported significantly lower pain intensity within the functional DMRI group (p = 0.01). However, there was no significant difference in pain intensity with the sub-functional DMRI group (p = 0.186). Conclusion The results suggest that gene variants in ABCB1 may potentially affect pain relief in opioid users, and may be useful in guiding opioid prescribing for pain management. Longitudinal pharmacogenetic studies in larger cohorts are necessary to establish the utility of such gene variants in ABCB1 in guiding safer and more effective pain management in patients with low back pain.

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