Document Detail


Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome.
MedLine Citation:
PMID:  17701031     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Neuroleptic malignant syndrome (NMS) is one of the most serious adverse reactions to antipsychotic medications. We accumulated data on Japanese NMS patients and, in a study designed to examine the effects of drug metabolism on the occurrence of NMS, tested the possibility of association between NMS and CYP2D6 polymorphisms. METHODS: We studied 53 patients who had experienced NMS and 112 healthy individuals. We determined what drugs the patients with NMS had been given and retrospectively identified candidates for drugs causing NMS. We screened the prevalence of CYP2D6 genotypes using polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: The prevalence of *5 alleles in the group of all patients with NMS was higher than that in the controls, though this difference was not statistically significant (10.4% vs. 5.4%; P = 0.107; odds ratio (OR) 2.05; 95% confidence interval (CI) 0.87-4.80). No association was found between the frequency of *10 alleles and the occurrence of NMS. We found *4 and duplicated alleles in only one patient each among the patients with NMS. A total of 29 patients appeared to have developed NMS as a result of having taking CYP2D6 substrates. The prevalence of *5 alleles in these 29 patient was significantly higher than that in the controls (15.5% vs. 5.4%; P = 0.020; OR 3.25; 95% CI 1.30-8.13). CONCLUSION: Our findings suggest that the CYP2D6*5 allele is likely to affect vulnerability to development of NMS.
Authors:
Daiji Kato; Chiaki Kawanishi; Ikuko Kishida; Taku Furuno; Kyoko Suzuki; Hideki Onishi; Yoshio Hirayasu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-14
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  63     ISSN:  0031-6970     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-11     Completed Date:  2008-02-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  991-6     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Alleles
Antipsychotic Agents / adverse effects*,  pharmacokinetics
Asian Continental Ancestry Group / genetics
Case-Control Studies
Child
Cytochrome P-450 CYP2D6 / genetics*,  metabolism
Female
Gene Deletion
Genotype
Humans
Japan
Male
Middle Aged
Neuroleptic Malignant Syndrome / genetics*
Odds Ratio
Polymorphism, Genetic*
Polymorphism, Restriction Fragment Length
Prevalence
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Antipsychotic Agents; EC 1.14.14.1/Cytochrome P-450 CYP2D6

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