The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases
Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one–third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopuri...
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| Format: | Article |
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Elsevier
2015-10-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315000535 |
| _version_ | 1828776281218482176 |
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| author | Hui Liu Liang Ding Fangbin Zhang Yu Zhang Xiang Gao Pinjin Hu Huichang Bi Min Huang |
| author_facet | Hui Liu Liang Ding Fangbin Zhang Yu Zhang Xiang Gao Pinjin Hu Huichang Bi Min Huang |
| author_sort | Hui Liu |
| collection | DOAJ |
| description | Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one–third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S–methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S–transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA–related ADRs in Chinese Han patients with IBD.
We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*–105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022–0.709, P = 0.0012).
The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST–P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA–related ADRs. |
| first_indexed | 2024-12-11T15:55:47Z |
| format | Article |
| id | doaj.art-bdf00cde111f43f1a17c02a9215cf84f |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T15:55:47Z |
| publishDate | 2015-10-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-bdf00cde111f43f1a17c02a9215cf84f2022-12-22T00:59:27ZengElsevierJournal of Pharmacological Sciences1347-86132015-10-0112929510010.1016/j.jphs.2015.02.013The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseasesHui Liu0Liang Ding1Fangbin Zhang2Yu Zhang3Xiang Gao4Pinjin Hu5Huichang Bi6Min Huang7Department of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou, PR ChinaInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat–sen University, Guangzhou, PR ChinaDepartment of Gastroenterology, the First Affiliated Hospital of Sun Yat–sen University, Guangzhou, PR ChinaInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat–sen University, Guangzhou, PR ChinaDepartment of Gastroenterology, the First Affiliated Hospital of Sun Yat–sen University, Guangzhou, PR ChinaDepartment of Gastroenterology, the First Affiliated Hospital of Sun Yat–sen University, Guangzhou, PR ChinaInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat–sen University, Guangzhou, PR ChinaInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat–sen University, Guangzhou, PR ChinaAzathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one–third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S–methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S–transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA–related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*–105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022–0.709, P = 0.0012). The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST–P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA–related ADRs.http://www.sciencedirect.com/science/article/pii/S1347861315000535AzathioprineInflammatory bowel diseaseGlutathione S-transferasesAdverse effects |
| spellingShingle | Hui Liu Liang Ding Fangbin Zhang Yu Zhang Xiang Gao Pinjin Hu Huichang Bi Min Huang The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases Journal of Pharmacological Sciences Azathioprine Inflammatory bowel disease Glutathione S-transferases Adverse effects |
| title | The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| title_full | The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| title_fullStr | The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| title_full_unstemmed | The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| title_short | The impact of glutathione S–transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| title_sort | impact of glutathione s transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases |
| topic | Azathioprine Inflammatory bowel disease Glutathione S-transferases Adverse effects |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315000535 |
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