Allele variants of the cytochrome P450 2C9 Genotype in white subjects from The Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs

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Abstract

Background: The most common serious adverse effects (AEs) associated with NSAID therapy are bleeding and perforated gastroduodenal ulcers. These AEs are dose related, and reduced oral clearance of NSAIDs associated with polymorphisms of cytochrome P450 (CYP) would, theoretically, increase the risk for AEs. Objective: The purpose of this study was to determine whether polymorphisms of the CYP2C9 genotype are associated with the development of serious complications of NSAID-related ulcers. Methods: We examined the records of patients with complications of serious NSAID-related ulcers who were hospitalized from November 2001 to December 2003. Diagnosis was confirmed by endoscopy or abdominal surgery, and a group of consecutive subjects was identified for genetic analysis. CYP2C9 allele frequencies were determined and compared with those in a matched cohort of subjects receiving stable weekly maintenance doses of oral coumarin anticoagulants. Allele frequencies also were compared with those in matched cohorts from earlier studies. Results: All 26 subjects with serious NSAID-related ulcers were white, 15 (58%) were female, and the median age was 74.5 years (range, 32–96 years). All 87 subjects in the reference group were white, 24 (28 %) were female, and the median age was 69 years (range, 48–81 years). CYP2C9 genotype frequencies did not differ significantly between subjects with serious complications of NSAID-related ulcers and subjects using oral coumarin anticoagulants. The genotype frequencies in both groups were similar to those reported in previous studies in white subjects. Conclusion: The CYP2C9 genotype was not a significant or clinically relevant risk factor in the development of serious NSAID-related ulcers in this group of subjects.
Original languageEnglish
Pages (from-to)1670-1676
JournalClinical therapeutics
Volume28
Issue number10
DOIs
Publication statusPublished - 2006

Fingerprint

Non-Steroidal Anti-Inflammatory Agents
Peptic Ulcer
Netherlands
Cytochrome P-450 Enzyme System
Alleles
Genotype
Ulcer
Gene Frequency
Anticoagulants
Endoscopy
Cohort Studies
Hemorrhage
Cytochrome P-450 CYP2C9

Keywords

  • NSAID
  • IR-71300
  • METIS-234777
  • ulcer
  • cytochrome P450
  • Polymorphism

Cite this

@article{ae1186ad21a14c5c9fbbd72fef930bda,
title = "Allele variants of the cytochrome P450 2C9 Genotype in white subjects from The Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs",
abstract = "Background: The most common serious adverse effects (AEs) associated with NSAID therapy are bleeding and perforated gastroduodenal ulcers. These AEs are dose related, and reduced oral clearance of NSAIDs associated with polymorphisms of cytochrome P450 (CYP) would, theoretically, increase the risk for AEs. Objective: The purpose of this study was to determine whether polymorphisms of the CYP2C9 genotype are associated with the development of serious complications of NSAID-related ulcers. Methods: We examined the records of patients with complications of serious NSAID-related ulcers who were hospitalized from November 2001 to December 2003. Diagnosis was confirmed by endoscopy or abdominal surgery, and a group of consecutive subjects was identified for genetic analysis. CYP2C9 allele frequencies were determined and compared with those in a matched cohort of subjects receiving stable weekly maintenance doses of oral coumarin anticoagulants. Allele frequencies also were compared with those in matched cohorts from earlier studies. Results: All 26 subjects with serious NSAID-related ulcers were white, 15 (58{\%}) were female, and the median age was 74.5 years (range, 32–96 years). All 87 subjects in the reference group were white, 24 (28 {\%}) were female, and the median age was 69 years (range, 48–81 years). CYP2C9 genotype frequencies did not differ significantly between subjects with serious complications of NSAID-related ulcers and subjects using oral coumarin anticoagulants. The genotype frequencies in both groups were similar to those reported in previous studies in white subjects. Conclusion: The CYP2C9 genotype was not a significant or clinically relevant risk factor in the development of serious NSAID-related ulcers in this group of subjects.",
keywords = "NSAID, IR-71300, METIS-234777, ulcer, cytochrome P450, Polymorphism",
author = "Vonkeman, {Harald Erwin} and {van de Laar}, {Mart A F J} and {van der Palen}, {Jacobus Adrianus Maria} and Brouwers, {Jacobus R.B.J.} and I. Vermes",
year = "2006",
doi = "10.1016/j.clinthera.2006.10.019",
language = "English",
volume = "28",
pages = "1670--1676",
journal = "Clinical therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
number = "10",

}

TY - JOUR

T1 - Allele variants of the cytochrome P450 2C9 Genotype in white subjects from The Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs

AU - Vonkeman, Harald Erwin

AU - van de Laar, Mart A F J

AU - van der Palen, Jacobus Adrianus Maria

AU - Brouwers, Jacobus R.B.J.

AU - Vermes, I.

PY - 2006

Y1 - 2006

N2 - Background: The most common serious adverse effects (AEs) associated with NSAID therapy are bleeding and perforated gastroduodenal ulcers. These AEs are dose related, and reduced oral clearance of NSAIDs associated with polymorphisms of cytochrome P450 (CYP) would, theoretically, increase the risk for AEs. Objective: The purpose of this study was to determine whether polymorphisms of the CYP2C9 genotype are associated with the development of serious complications of NSAID-related ulcers. Methods: We examined the records of patients with complications of serious NSAID-related ulcers who were hospitalized from November 2001 to December 2003. Diagnosis was confirmed by endoscopy or abdominal surgery, and a group of consecutive subjects was identified for genetic analysis. CYP2C9 allele frequencies were determined and compared with those in a matched cohort of subjects receiving stable weekly maintenance doses of oral coumarin anticoagulants. Allele frequencies also were compared with those in matched cohorts from earlier studies. Results: All 26 subjects with serious NSAID-related ulcers were white, 15 (58%) were female, and the median age was 74.5 years (range, 32–96 years). All 87 subjects in the reference group were white, 24 (28 %) were female, and the median age was 69 years (range, 48–81 years). CYP2C9 genotype frequencies did not differ significantly between subjects with serious complications of NSAID-related ulcers and subjects using oral coumarin anticoagulants. The genotype frequencies in both groups were similar to those reported in previous studies in white subjects. Conclusion: The CYP2C9 genotype was not a significant or clinically relevant risk factor in the development of serious NSAID-related ulcers in this group of subjects.

AB - Background: The most common serious adverse effects (AEs) associated with NSAID therapy are bleeding and perforated gastroduodenal ulcers. These AEs are dose related, and reduced oral clearance of NSAIDs associated with polymorphisms of cytochrome P450 (CYP) would, theoretically, increase the risk for AEs. Objective: The purpose of this study was to determine whether polymorphisms of the CYP2C9 genotype are associated with the development of serious complications of NSAID-related ulcers. Methods: We examined the records of patients with complications of serious NSAID-related ulcers who were hospitalized from November 2001 to December 2003. Diagnosis was confirmed by endoscopy or abdominal surgery, and a group of consecutive subjects was identified for genetic analysis. CYP2C9 allele frequencies were determined and compared with those in a matched cohort of subjects receiving stable weekly maintenance doses of oral coumarin anticoagulants. Allele frequencies also were compared with those in matched cohorts from earlier studies. Results: All 26 subjects with serious NSAID-related ulcers were white, 15 (58%) were female, and the median age was 74.5 years (range, 32–96 years). All 87 subjects in the reference group were white, 24 (28 %) were female, and the median age was 69 years (range, 48–81 years). CYP2C9 genotype frequencies did not differ significantly between subjects with serious complications of NSAID-related ulcers and subjects using oral coumarin anticoagulants. The genotype frequencies in both groups were similar to those reported in previous studies in white subjects. Conclusion: The CYP2C9 genotype was not a significant or clinically relevant risk factor in the development of serious NSAID-related ulcers in this group of subjects.

KW - NSAID

KW - IR-71300

KW - METIS-234777

KW - ulcer

KW - cytochrome P450

KW - Polymorphism

U2 - 10.1016/j.clinthera.2006.10.019

DO - 10.1016/j.clinthera.2006.10.019

M3 - Article

VL - 28

SP - 1670

EP - 1676

JO - Clinical therapeutics

JF - Clinical therapeutics

SN - 0149-2918

IS - 10

ER -