Abstract:
BACKGROUND:Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%-38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glutathione-S-transferase (GST) activity compared with those with low activity; moreover, some reports indicate that GST might play a direct role in the reaction of glutathione with azathioprine. The association between polymorphisms of GST-M1, GST-P1, GST-T1, and TPMT genes and the adverse effects of azathioprine was therefore investigated. METHODS:Seventy patients with inflammatory bowel disease (IBD), treated with azathioprine, were enrolled and clinical data were retrospectively determined. TPMT and GST genotyping were performed by polymerase chain reaction (PCR) assays on DNA extracted from blood samples. RESULTS:Fifteen patients developed adverse effects (21.4%); there was a significant underrepresentation of the GST-M1 null genotype among patients developing adverse drug reactions to azathioprine (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.037-0.72, P = 0.0072) compared with patients who did not develop adverse effects. Patients heterozygous for TPMT mutations presented a marginally significant increased probability of developing adverse effects (OR = 6.38, 95% CI = 0.66-84.1, P = 0.062). Moreover, among the 55 patients who did not develop adverse effects, there was a significant underrepresentation of the GST-M1 null genotype among patients who displayed lymphopenia as compared with those that did not display this effect of azathioprine (OR = 0.15, 95% CI = 0.013-1.08, P = 0.032). CONCLUSION:Patients with IBD with a wildtype GST-M1 genotype present increased probability of developing adverse effects and increased incidence of lymphopenia during azathioprine treatment.
journal_name
Inflamm Bowel Disjournal_title
Inflammatory bowel diseasesauthors
Stocco G,Martelossi S,Barabino A,Decorti G,Bartoli F,Montico M,Gotti A,Ventura Adoi
10.1002/ibd.20004subject
Has Abstractpub_date
2007-01-01 00:00:00pages
57-64issue
1eissn
1078-0998issn
1536-4844journal_volume
13pub_type
杂志文章abstract::Natural killer T (NKT) cells are a subset of lymphocytes that express cell surface molecules of both conventional T cells and natural killer cells and share the features of both innate and adaptive immune cells. NKT cells have been proposed to make both protective and pathogenic contributions to inflammatory bowel dis...
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pub_type: 临床试验,杂志文章
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journal_title:Inflammatory bowel diseases
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Inflammatory bowel diseases
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doi:10.1097/01.mib.0000235830.94057.c6
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pub_type: 杂志文章
doi:10.1097/01.mib.0000186485.30623.ad
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更新日期:2012-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/ibd.20530
更新日期:2008-12-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1002/ibd.20280
更新日期:2008-02-01 00:00:00
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,评审
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21442
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章,meta分析
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.21265
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pub_type: 杂志文章,meta分析,评审
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journal_title:Inflammatory bowel diseases
pub_type: 杂志文章
doi:10.1002/ibd.23006
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journal_title:Inflammatory bowel diseases
pub_type: 临床试验,杂志文章
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