title: Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6.
abstract: BACKGROUND
  Cytochrome P450 2D6 (CYP2D6) is responsible for the metabolism of clinically used drugs and other environmental exposures, but it is unclear whether theCYP2D6phenotype is associated with adverse health outcomes. The aim was to determine the association ofCYP2D6phenotype 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 underwentCYP2D6testing. The primary outcome was risk of hospitalization or an ED visit from January 2005 through September 2014.CYP2D6genotypes 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 ofCYP2D6phenotypes 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).
  
  
  CONCLUSIONS
  We found an increased risk of hospitalization or an ED visit among ultrarapid compared to extensiveCYP2D6metabolizers. Further research identifying the mechanisms of the association and ultimate clinical utility is warranted.
authors.affiliation: Division of Primary Care Internal Medicine, Department of Medicine.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Takahashi
authors.affiliation: Department of Health Sciences Research.
authors.forename: Euijung
authors.initials: E
authors.lastname: Ryu
authors.affiliation: Department of Health Sciences Research.
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.affiliation: Department of Health Sciences Research.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Jenkins
authors.affiliation: Department of Health Sciences Research.
authors.forename: Anthony
authors.initials: A
authors.lastname: Batzler
authors.affiliation: Department of Health Sciences Research.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hathcock
authors.affiliation: Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John Logan
authors.initials: JL
authors.lastname: Black
authors.affiliation: Department of Health Sciences Research.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.affiliation: Department of Health Sciences Research.
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.affiliation: Department of Health Sciences Research.
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
keywords: cohort study; emergency department; hospitalization; pharmacogenomics