Khalil, Heba
(2015)
OPRM1 and COMT Gene-Gene Interaction Effects on the
Inter-individual Variability in Postoperative Pain and Response to Opioids.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Background: Treatment of postoperative pain remains suboptimal. This is attributed, in part, to the individualized physiological and psychological perception of pain. Although the effect of genetic variation on pain is unequivocal, precise understating of the effect of multiple gene interaction is yet to be investigated. Catechol-O-methyltransferase (COMT) interacts with several neuroreceptors in the brain including the mu receptor (OPRM1). Hence, we sought to explore the gene-gene interaction effect of OPRM1 and COMT on postoperative pain and opioid dose required for pain management. Methods: We used genotypes and clinical data for 153 postoperative orthopedic trauma patients. For the COMT gene four single nucleotide polymorphisms (rs6269, rs4633, rs4818 and rs4680), three haplotypes (ACCG, ATCA, and GCGG), and two diplotypes (low and high pain intensity) were considered for their interactions with A118G of OPRM1 on postoperative pain and opioid consumption. Data were analyzed using descriptive statistics and multiple regression. Analyses were repeated including only the Caucasian subjects. Results: For postoperative opioid consumption; a significant interaction was found between OPRM1 and COMT rs4680 (b=0.093, p=.037) and OPRM1 and COMT rs4633 (b=0.097, p=.037). The interactions between OPRM1 and COMT rs6269 and OPRM1 and COMT diplotypes demonstrated trends toward significance (b=-0.075, p=.080 and b=0.071, p=.070, respectively). The results for OPRM1×COMT rs4680 and OPRM1×COMT rs4633 on opioid consumption were maintained even after restricting the analyses to only Caucasian subjects. For postoperative pain scores, a significant interaction was found between OPRM1 and the GCGG haplotype of COMT (b=-0.926, p=.017). The interaction between OPRM1 and COMT rs4818 demonstrated a trend (b=-0.755, p=.060). When the sample was limited to only Caucasian subjects, only a trend was observed for the interaction effect of OPRM1 and the GCGG haplotype of COMT on postoperative pain (p= .070). The interactions of OPRM1×ACCG haplotype and OPRM1×diplotypes of COMT also showed trends toward significance (b=1.110, p= .058 and b=0.831, p= .050, respectively). Conclusion: OPRM1×COMT interactions may influence the variability in postoperative pain and response to opioids. Individualized pain management based on genetic variation can be an effective strategy to maximize the usefulness of pain management.
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| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
15 December 2015 |
| Date Type: |
Publication |
| Defense Date: |
18 November 2015 |
| Approval Date: |
15 December 2015 |
| Submission Date: |
13 December 2015 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
130 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Nursing > Nursing |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Gene-gene interaction; OPRM1; COMT; Postoperative pain, Opioid analgesia |
| Date Deposited: |
15 Dec 2015 17:13 |
| Last Modified: |
15 Nov 2016 14:31 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/26662 |
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