Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis and Genomic Information
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
EGD | Esophagogastroduodenoscopy |
CYP450 | Cytochromes P450 |
PGRN | Pharmacogenomics Research Network |
SNPs | Single nucleotide polymorphisms |
OR | Odds ratio |
CI | Confidence interval |
BMI | Body mass index |
IRB | Institutional Review Board |
HSD | High sedation |
NSD | Normal sedation |
References
- Matey, E.T.; Ragan, A.K.; Oyen, L.J.; Vitek, C.R.; Aoudia, S.L.; Ragab, A.K.; Fee-Schroeder, K.C.; Black, J.L.; Moyer, A.M.; Nicholson, W.T.; et al. Nine-gene pharmacogenomics profile service: The Mayo Clinic experience. Pharm. J. 2022, 22, 69–74. [Google Scholar] [CrossRef] [PubMed]
- Jun, J.; Han, J.I.; Choi, A.L.; Kim, Y.J.; Lee, J.W.; Kim, D.Y.; Lee, M. Adverse events of conscious sedation using midazolam for gastrointestinal endoscopy. Anesth. Pain Med. 2019, 14, 401–406. [Google Scholar] [CrossRef] [PubMed]
- El Rouby, N.; Lima, J.J.; Johnson, J.A. Proton pump inhibitors: From CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab. Toxicol. 2018, 14, 447–460. [Google Scholar] [CrossRef] [PubMed]
- Claassens, D.M.F.; Vos, G.J.A.; Bergmeijer, T.O.; Hermanides, R.S.; van ‘t Hof, A.W.J.; van der Harst, P.; Barbato, E.; Morisco, C.; Tjon Joe Gin, R.M.; Asselbergs, F.W.; et al. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N. Engl. J. Med. 2019, 381, 1621–1631. [Google Scholar] [CrossRef] [PubMed]
- Pirmohamed, M.; Burnside, G.; Eriksson, N.; Jorgensen, A.L.; Toh, C.H.; Nicholson, T.; Kesteven, P.; Christersson, C.; Wahlstrom, B.; Stafberg, C.; et al. A randomized trial of genotype-guided dosing of warfarin. N. Engl. J. Med. 2013, 369, 2294–2303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bielinski, S.J.; Olson, J.E.; Pathak, J.; Weinshilboum, R.M.; Wang, L.; Lyke, K.J.; Ryu, E.; Targonski, P.V.; Van Norstrand, M.D.; Hathcock, M.A.; et al. Preemptive genotyping for personalized medicine: Design of the right drug, right dose, right time-using genomic data to individualize treatment protocol. Mayo Clin. Proc. 2014, 89, 25–33. [Google Scholar] [CrossRef] [PubMed]
- Bielinski, S.J.; St Sauver, J.L.; Olson, J.E.; Larson, N.B.; Black, J.L.; Scherer, S.E.; Bernard, M.E.; Boerwinkle, E.; Borah, B.J.; Caraballo, P.J.; et al. Cohort Profile: The Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment Protocol (RIGHT Protocol). Int. J. Epidemiol. 2020, 49, 23–24k. [Google Scholar] [CrossRef] [PubMed]
- Horn, E.; Nesbit, S.A. Pharmacology and pharmacokinetics of sedatives and analgesics. Gastrointest. Endosc. Clin. N. Am. 2004, 14, 247–268. [Google Scholar] [CrossRef] [PubMed]
- Moon, S.H. Sedation regimens for gastrointestinal endoscopy. Clin. Endosc. 2014, 47, 135–140. [Google Scholar] [CrossRef] [PubMed]
- Gaedigk, A.; Ingelman-Sundberg, M.; Miller, N.A.; Leeder, J.S.; Whirl-Carrillo, M.; Klein, T.E.; PharmVar Steering, C. The Pharmacogene Variation (PharmVar) Consortium: Incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database. Clin. Pharmacol. Ther. 2018, 103, 399–401. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- (Gaedigk et al. 2018, C.G.e.a., CPT 105:29). Pharmacogene Variation Consortium (PharmVar). Available online: https://www.pharmvar.org/ (accessed on 26 June 2023).
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–424. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, S.; Chan, E.; Li, X.; Huang, M. Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4. Ther. Clin. Risk Manag. 2005, 1, 3–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Whirl-Carrillo, M.; Huddart, R.; Gong, L.; Sangkuhl, K.; Thorn, C.F.; Whaley, R.; Klein, T.E. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin. Pharmacol. Ther. 2021, 110, 563–572. [Google Scholar] [CrossRef] [PubMed]
- Whirl-Carrillo, M.; McDonagh, E.M.; Hebert, J.M.; Gong, L.; Sangkuhl, K.; Thorn, C.F.; Altman, R.B.; Klein, T.E. Pharmacogenomics knowledge for personalized medicine. Clin. Pharmacol. Ther. 2012, 92, 414–417. [Google Scholar] [CrossRef] [PubMed]
- Takano, M.; Sugiyama, T. UGT1A1 polymorphisms in cancer: Impact on irinotecan treatment. Pharmgenomics Pers. Med. 2017, 10, 61–68. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hamaoka, N.; Oda, Y.; Hase, I.; Asada, A. Cytochrome P4502B6 and 2C9 do not metabolize midazolam: Kinetic analysis and inhibition study with monoclonal antibodies. Br. J. Anaesth. 2001, 86, 540–544. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oda, Y.; Mizutani, K.; Hase, I.; Nakamoto, T.; Hamaoka, N.; Asada, A. Fentanyl inhibits metabolism of midazolam: Competitive inhibition of CYP3A4 in vitro. Br. J. Anaesth. 1999, 82, 900–903. [Google Scholar] [CrossRef] [PubMed]
Normal Sedation (N = 123) | High Sedation (N = 89) | Total (N = 212) | p Value | |
---|---|---|---|---|
Age at time of procedure | <0.0001 | |||
Mean (SD) | 73.1 (7.3) | 67.8 (8.8) | 70.9 (8.4) | |
Median | 73.9 | 69.6 | 72.5 | |
Q1, Q3 | 70.3, 76.5 | 62.7, 74.8 | 67.8, 76.2 | |
Range | (43.6–116.5) | (46.4–80.1) | (43.6–116.5) | |
Patient sex | 0.5149 | |||
F | 58 (47.2%) | 46 (51.7%) | 104 (49.1%) | |
M | 65 (52.8%) | 43 (48.3%) | 108 (50.9%) | |
Race | 0.8174 | |||
White | 122 (99.2%) | 88 (98.9%) | 210 (99.1%) | |
Mixed | 1 (0.8%) | 1 (1.1%) | 2 (0.9%) | |
BMI | 0.5614 | |||
N | 123 | 89 | 212 | |
Mean (SD) | 28.1 (6.1) | 27.6 (9.7) | 27.9 (7.8) | |
Median | 28.0 | 28.3 | 28.0 | |
Q1, Q3 | 25.1, 31.3 | 26.2, 31.2 | 25.5, 31.2 | |
Range | (0.0–52.5) | (0.0–66.6) | (0.0–66.6) | |
Procedure | 0.1546 | |||
Colonoscopy | 86 (69.9%) | 70 (78.7%) | 156 (73.6%) | |
EGD | 37 (30.1%) | 19 (21.3%) | 56 (26.4%) | |
Which procedure came first | 0.3127 | |||
Colonoscopy | 100 (81.3%) | 77 (86.5%) | 177 (83.5%) | |
EGD | 23 (18.7%) | 12 (13.5%) | 35 (16.5%) | |
Polyp | 0.4020 | |||
Missing | 33 (26.8%) | 17 (19.1%) | 50 (23.6%) | |
No | 22 (17.9%) | 16 (18.0%) | 38 (17.9%) | |
Yes | 68 (55.3%) | 56 (62.9%) | 124 (58.5%) | |
Number of polyps | 0.1618 | |||
N | 68 | 56 | 124 | |
Mean (SD) | 1.9 (1.1) | 2.2 (1.3) | 2.0 (1.2) | |
Median | 2.0 | 2.0 | 2.0 | |
Q1, Q3 | 1.0, 2.5 | 1.0, 3.0 | 1.0, 3.0 | |
Range | (1.0–5.0) | (1.0–7.0) | (1.0–7.0) | |
Biopsies | 0.0817 | |||
Missing | 68 (55.3%) | 60 (67.4%) | 128 (60.4%) | |
No | 10 (8.1%) | 2 (2.2%) | 12 (5.7%) | |
Yes | 45 (36.6%) | 27 (30.3%) | 72 (34.0%) | |
Total duration of procedures (minutes) | 0.0102 | |||
N | 118 | 89 | 207 | |
Mean (SD) | 20.8 (13.8) | 24.6 (12.2) | 22.4 (13.3) | |
Median | 18.0 | 24.0 | 21.0 | |
Q1, Q3 | 9.0, 29.0 | 16.0, 31.0 | 12.0, 30.0 | |
Range | (3.0–68.0) | (4.0–70.0) | (3.0–70.0) |
Normal (N = 123) | High (N = 89) | OR (95% CIs) | p Value a | |
---|---|---|---|---|
CYP1A2 | ||||
Reduced metabolism (intermediate + normal metabolizers) | 8 | 9 | 1.00 (ref) | |
Increased metabolism (rapid metabolizers) | 115 | 80 | 0.16 (1.16–1.34) | 0.16 |
CYP2C19 | ||||
Normal metabolizer | 53 | 40 | 1.00 (ref) | |
Reduced metabolism (poor + intermediate metabolizers) | 32 | 11 | 0.38 (0.16–0.91) | 0.03 |
Increased metabolism (rapid + ultrarapid metabolizers) | 38 | 38 | 1.16 (0.60–2.22) | 0.66 |
CYP2C9 | ||||
Normal metabolizer | 77 | 52 | 1.00 (ref) | |
Intermediate metabolizer | 46 | 37 | 1.20 (0.66–2.19) | 0.55 |
CYP2D6 | ||||
Normal metabolizer | 39 | 32 | 1.00 (ref) | |
Reduced metabolism (poor + intermediate metabolizers) | 81 | 57 | 0.80 (0.43–1.47) | 0.47 |
Increased metabolism (ultrarapid metabolizers) | 3 | 0 | NE | |
CYP3A4 | ||||
Normal metabolizer | 112 | 79 | 1.00 (ref) | |
Reduced metabolism (poor + intermediate metabolizers) | 11 | 10 | 1.57 (0.61–4.03) | 0.34 |
CYP3A5 | ||||
Intermediate metabolizer | 8 | 16 | 1.00 (ref) | |
Poor metabolizer | 115 | 73 | 0.25 (0.095–0.65) | 0.0046 |
UGT1A1 | ||||
Normal metabolizer | 61 | 35 | 1.00 (ref) | |
Intermediate metabolizer | 51 | 41 | 1.65 (0.87–3.13) | 0.12 |
Poor metabolizer | 11 | 13 | 2.76 (1.07–7.13) | 0.08 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zaver, H.B.; Ghoz, H.; Malviya, B.; Bali, A.; Antwi, S.; Moyer, A.M.; Bi, Y. Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation? J. Pers. Med. 2023, 13, 1107. https://0-doi-org.brum.beds.ac.uk/10.3390/jpm13071107
Zaver HB, Ghoz H, Malviya B, Bali A, Antwi S, Moyer AM, Bi Y. Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation? Journal of Personalized Medicine. 2023; 13(7):1107. https://0-doi-org.brum.beds.ac.uk/10.3390/jpm13071107
Chicago/Turabian StyleZaver, Himesh B., Hassan Ghoz, Balkishan Malviya, Aman Bali, Samuel Antwi, Ann M. Moyer, and Yan Bi. 2023. "Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?" Journal of Personalized Medicine 13, no. 7: 1107. https://0-doi-org.brum.beds.ac.uk/10.3390/jpm13071107