PMID- 17157122
OWN - NLM
STAT- MEDLINE
DCOM- 20070213
LR  - 20221207
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 28
IP  - 10
DP  - 2006 Oct
TI  - Allele variants of the cytochrome P450 2C9 genotype in white subjects from The 
      Netherlands with serious gastroduodenal ulcers attributable to the use of NSAIDs.
PG  - 1670-6
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.
FAU - Vonkeman, Harald E
AU  - Vonkeman HE
AD  - Department of Rheumatolog and Clinical Immunoloy, Medisch Spectrum Twente 
      Hospital, University of Twente, Enschede, The Netherlands. 
      H.Vonkeman@ziekenhuis-mst.nl
FAU - van de Laar, Mart A F J
AU  - van de Laar MA
FAU - van der Palen, Job
AU  - van der Palen J
FAU - Brouwers, Jacobus R B J
AU  - Brouwers JR
FAU - Vermes, Istvan
AU  - Vermes I
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Alleles
MH  - Anti-Inflammatory Agents, Non-Steroidal/*adverse effects
MH  - Aryl Hydrocarbon Hydroxylases/*genetics
MH  - Cohort Studies
MH  - Cytochrome P-450 CYP2C9
MH  - Duodenal Ulcer/*chemically induced/genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Netherlands
MH  - Stomach Ulcer/*chemically induced/genetics
MH  - White People/*genetics
EDAT- 2006/12/13 09:00
MHDA- 2007/02/14 09:00
CRDT- 2006/12/13 09:00
PHST- 2006/08/20 00:00 [accepted]
PHST- 2006/12/13 09:00 [pubmed]
PHST- 2007/02/14 09:00 [medline]
PHST- 2006/12/13 09:00 [entrez]
AID - S0149-2918(06)00259-1 [pii]
AID - 10.1016/j.clinthera.2006.10.019 [doi]
PST - ppublish
SO  - Clin Ther. 2006 Oct;28(10):1670-6. doi: 10.1016/j.clinthera.2006.10.019.