Document Detail


Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study.
MedLine Citation:
PMID:  20308917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIM: Myelotoxicity has been shown to be very common in Korean patients with inflammatory bowel disease (IBD) during azathioprine (AZA) or 6-mercaptopurine (6-MP) treatment. The purpose of this study was to investigate the relative risk of the thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genotypes and TPMT activity for the development of leukopenia in Korean IBD patients during AZA/6-MP treatment.
METHODS: We retrospectively analyzed 286 Korean patients with IBD who had been treated with AZA/6-MP for at least 6 months between June 1996 and September 2006. Common TPMT mutations, including TPMT*1, *2, *3A, *3B, and *3C, and ITPA mutations, including 94C>A and IVS2+21A>C, were determined using a high-performance liquid chromatography method. TPMT activity was measured using liquid chromatography with coupled mass spectrometry/mass spectrometry.
RESULTS: Leukopenia occurred in 118 cases (41.3%). TPMT *1/*3C was detected in 7 cases (2.4%), and ITPA 94 C>A was detected in 66 cases (23.1%), including 63 heterozygotes (22.1%) and 3 homozygotes (1.0%). The median TPMT activity was 9.3 U/mL (interquartile range 10.4, range 2.1 to 76.2). Cox regression analysis revealed that patients with heterozygous *3C type TPMT had a higher probability of leukopenia than those with wild type TPMT (P=0.02). Patients with intermediate TPMT activity had a lower probability of leukopenia than those with low activity (P=0.01). However, the ITPA genotype did not affect the risk of leukopenia.
CONCLUSIONS: Our data showed that it could be helpful to examine TPMT genotypes and to measure TPMT activity in Korean patients taking AZA/6-MP to predict the development of leukopenia.
Authors:
Jae Hak Kim; Jae Hee Cheon; Seong Soo Hong; Chang Soo Eun; Jeong-Sik Byeon; Sung Yi Hong; Bo-Young Kim; Soon-Ho Kwon; Seung Won Kim; Dong Soo Han; Suk-Kyun Yang; Won Ho Kim
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Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical gastroenterology     Volume:  44     ISSN:  1539-2031     ISO Abbreviation:  J. Clin. Gastroenterol.     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-02-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7910017     Medline TA:  J Clin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e242-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Dongguk University College of Medicine, Goyang-si, Korea.
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MeSH Terms
Descriptor/Qualifier:
6-Mercaptopurine / adverse effects*,  analogs & derivatives*,  pharmacokinetics
Academic Medical Centers
Adolescent
Adult
Anti-Inflammatory Agents / adverse effects*,  pharmacokinetics
Asian Continental Ancestry Group / genetics*
Chi-Square Distribution
Chromatography, High Pressure Liquid
Female
Gastrointestinal Agents / adverse effects*,  pharmacokinetics
Genetic Predisposition to Disease
Heterozygote
Homozygote
Humans
Inflammatory Bowel Diseases / drug therapy*,  enzymology,  ethnology,  genetics
Kaplan-Meier Estimate
Leukopenia / chemically induced*,  ethnology,  genetics
Male
Methyltransferases / genetics,  metabolism*
Phenotype
Proportional Hazards Models
Pyrophosphatases / genetics,  metabolism
Republic of Korea
Retrospective Studies
Risk Assessment
Risk Factors
Tandem Mass Spectrometry
Treatment Outcome
Young Adult
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Gastrointestinal Agents; 0/azathiopurine; 50-44-2/6-Mercaptopurine; EC 2.1.1.-/Methyltransferases; EC 2.1.1.67/thiopurine methyltransferase; EC 3.6.1.-/Pyrophosphatases; EC 3.6.1.19/ITPA protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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