Cargando…
Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6
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...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317339/ https://www.ncbi.nlm.nih.gov/pubmed/28243137 http://dx.doi.org/10.2147/PGPM.S114211 |
_version_ | 1782508986385301504 |
---|---|
author | Takahashi, Paul Y Ryu, Euijung Pathak, Jyotishman Jenkins, Gregory D Batzler, Anthony Hathcock, Matthew A Black, John Logan Olson, Janet E Cerhan, James R Bielinski, Suzette J |
author_facet | Takahashi, Paul Y Ryu, Euijung Pathak, Jyotishman Jenkins, Gregory D Batzler, Anthony Hathcock, Matthew A Black, John Logan Olson, Janet E Cerhan, James R Bielinski, Suzette J |
author_sort | Takahashi, Paul Y |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5317339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53173392017-02-27 Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 Takahashi, Paul Y Ryu, Euijung Pathak, Jyotishman Jenkins, Gregory D Batzler, Anthony Hathcock, Matthew A Black, John Logan Olson, Janet E Cerhan, James R Bielinski, Suzette J Pharmgenomics Pers Med Original Research 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. Dove Medical Press 2017-02-14 /pmc/articles/PMC5317339/ /pubmed/28243137 http://dx.doi.org/10.2147/PGPM.S114211 Text en © 2017 Takahashi et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Takahashi, Paul Y Ryu, Euijung Pathak, Jyotishman Jenkins, Gregory D Batzler, Anthony Hathcock, Matthew A Black, John Logan Olson, Janet E Cerhan, James R Bielinski, Suzette J Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title | Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title_full | Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title_fullStr | Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title_full_unstemmed | Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title_short | Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6 |
title_sort | increased risk of hospitalization for ultrarapid metabolizers of cytochrome p450 2d6 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317339/ https://www.ncbi.nlm.nih.gov/pubmed/28243137 http://dx.doi.org/10.2147/PGPM.S114211 |
work_keys_str_mv | AT takahashipauly increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT ryueuijung increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT pathakjyotishman increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT jenkinsgregoryd increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT batzleranthony increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT hathcockmatthewa increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT blackjohnlogan increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT olsonjanete increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT cerhanjamesr increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 AT bielinskisuzettej increasedriskofhospitalizationforultrarapidmetabolizersofcytochromep4502d6 |