Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6
Authors Takahashi PY, Ryu E, Pathak J, Jenkins GD, Batzler A, Hathcock MA, Black JL, Olson JE, Cerhan JR, Bielinski SJ
Received 3 June 2016
Accepted for publication 27 September 2016
Published 14 February 2017 Volume 2017:10 Pages 39—47
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 3
Editor who approved publication: Dr Martin H. Bluth
Paul Y Takahashi,1 Euijung Ryu,2 Jyotishman Pathak,2 Gregory D Jenkins,2 Anthony Batzler,2 Matthew A Hathcock,2 John Logan Black,3 Janet E Olson,2 James R Cerhan,2 Suzette J Bielinski2
1Division of Primary Care Internal Medicine, Department of Medicine, 2Department of Health Sciences Research, 3Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Background: Cytochrome P450 2D6 (CYP2D6) is responsible for the metabolism of clinically used drugs and other environmental exposures, but it is unclear whether the CYP2D6 phenotype is associated with adverse health outcomes. The aim was to determine the association of CYP2D6 phenotype with the risk of hospitalization or an emergency department (ED) visit among a group of primary care patients.
Methods: In this study, 929 adult patients underwent CYP2D6 testing. The primary outcome was risk of hospitalization or an ED visit from January 2005 through September 2014. CYP2D6 genotypes were interpreted as 1 of 7 clinical phenotypes, from ultrarapid to poor metabolizer, and patients with the extensive metabolizer phenotype were used as the reference group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for finding the association of CYP2D6 phenotypes with the risk of hospitalization or an ED visit by using Cox proportional hazard models and adjusting for age and sex.
Results: The median age was 49 years (interquartile range, 46–52 years); 74% of patients had 3 or fewer chronic conditions, 285 had at least 1 hospitalization, and 496 had at least 1 ED visit. The risk of hospitalization was higher among patients who were ultrarapid metabolizers compared to extensive metabolizers (47% vs 30%; HR, 1.69; 95% CI, 1.11–2.57), as was the risk of an ED visit (62% vs 49%; HR, 1.50; 95% CI, 1.05–2.14). For poor metabolizers compared to extensive metabolizers, there was no difference in the risk of hospitalization (HR, 0.95; 95% CI, 0.58–1.56), but there was an increase in the risk of an ED visit (HR, 1.38; 95% CI, 0.96–1.98) (the difference was not statistically significant).
Conclusion: We found an increased risk of hospitalization or an ED visit among ultrarapid compared to extensive CYP2D6 metabolizers. Further research identifying the mechanisms of the association and ultimate clinical utility is warranted.
Keywords: cohort study, pharmacogenomics, emergency department, hospitalization
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