About: Gene Polymorphisms Involved in Manifestation of Leucopenia, Digestive Intolerance, and Pancreatitis in Azathioprine-Treated Patients     Goto   Sponge   NotDistinct   Permalink

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  • Approximately 10-28 % of patients experience adverse drug reactions related to treatment with thiopurines. The most serious reaction is myelosuppression, typically manifested as leucopenia, which occurs in approximately 2-5 % of patients. Other adverse drug reactions that often accompany thiopurine therapy are pancreatitis, hepatotoxicity, allergic reactions, digestive intolerance, arthralgia, febrile conditions, and rash. The objective of this study was to assess the relationship between variant alleles of thiopurine S-methyltransferase (SNPs 238G } C, 460G } A and 719A } G), inosine triphosphate diphosphatase (SNPs 94C } A and IVS2 + 21A } C), and xanthine dehydrogenase (837C } T) and the occurrence of adverse drug reactions to azathioprine therapy. Genotype was determined for 188 Caucasians diagnosed with inflammatory bowel disease treated with a standard dose of azathioprine (1.4-2.0 mg/kg/day). Variant genotype thiopurine S-methyltransferase predisposes to development of leucopenia (P = 0.003, OR = 5, CI 95 %, 1.8058-13.8444). Although not statistically significant, we observed a trend that suggested correlation between the occurrence of digestive intolerance and the variant genotype inosine triphosphate diphosphatase (P = 0.1102; OR 15.63, CI 95 %, 1.162-210.1094), and between the occurrence of pancreatitis and the variant allele xanthine dehydrogenase 837T (P = 0.1124; OR 12,1, CI 95 %, 1.15-126.37). The variant genotype thiopurine S-methyltransferase has been associated with the occurrence of leucopenia. The involvement of polymorphisms in inosine triphosphate diphosphatase and xanthine dehydrogenase genes in the development of digestive intolerance and pancreatitis will require further verification.
  • Approximately 10-28 % of patients experience adverse drug reactions related to treatment with thiopurines. The most serious reaction is myelosuppression, typically manifested as leucopenia, which occurs in approximately 2-5 % of patients. Other adverse drug reactions that often accompany thiopurine therapy are pancreatitis, hepatotoxicity, allergic reactions, digestive intolerance, arthralgia, febrile conditions, and rash. The objective of this study was to assess the relationship between variant alleles of thiopurine S-methyltransferase (SNPs 238G } C, 460G } A and 719A } G), inosine triphosphate diphosphatase (SNPs 94C } A and IVS2 + 21A } C), and xanthine dehydrogenase (837C } T) and the occurrence of adverse drug reactions to azathioprine therapy. Genotype was determined for 188 Caucasians diagnosed with inflammatory bowel disease treated with a standard dose of azathioprine (1.4-2.0 mg/kg/day). Variant genotype thiopurine S-methyltransferase predisposes to development of leucopenia (P = 0.003, OR = 5, CI 95 %, 1.8058-13.8444). Although not statistically significant, we observed a trend that suggested correlation between the occurrence of digestive intolerance and the variant genotype inosine triphosphate diphosphatase (P = 0.1102; OR 15.63, CI 95 %, 1.162-210.1094), and between the occurrence of pancreatitis and the variant allele xanthine dehydrogenase 837T (P = 0.1124; OR 12,1, CI 95 %, 1.15-126.37). The variant genotype thiopurine S-methyltransferase has been associated with the occurrence of leucopenia. The involvement of polymorphisms in inosine triphosphate diphosphatase and xanthine dehydrogenase genes in the development of digestive intolerance and pancreatitis will require further verification. (en)
Title
  • Gene Polymorphisms Involved in Manifestation of Leucopenia, Digestive Intolerance, and Pancreatitis in Azathioprine-Treated Patients
  • Gene Polymorphisms Involved in Manifestation of Leucopenia, Digestive Intolerance, and Pancreatitis in Azathioprine-Treated Patients (en)
skos:prefLabel
  • Gene Polymorphisms Involved in Manifestation of Leucopenia, Digestive Intolerance, and Pancreatitis in Azathioprine-Treated Patients
  • Gene Polymorphisms Involved in Manifestation of Leucopenia, Digestive Intolerance, and Pancreatitis in Azathioprine-Treated Patients (en)
skos:notation
  • RIV/62157124:16370/12:43871450!RIV13-MSM-16370___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
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  • P(FR-TI2/075), P(NR9342), S
http://linked.open...iv/cisloPeriodika
  • 9
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  • 137799
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  • RIV/62157124:16370/12:43871450
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  • Pharmacogenomics; Xanthine dehydrogenase; Thiopurine S-methyltransferase; Inosine triphosphate diphosphatase; Inflammatory bowel disease; Azathioprine (en)
http://linked.open.../riv/klicoveSlovo
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  • NL - Nizozemsko
http://linked.open...ontrolniKodProRIV
  • [A8D7659265B2]
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  • Digestive Diseases and Sciences
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...v/svazekPeriodika
  • 57
http://linked.open...iv/tvurceVysledku
  • Zbořil, Vladimír
  • Bartoš, Milan
  • Bartošová, Ladislava
  • Kolorz, Michal
  • Uličný, Boris
  • Wróblová, Kateřina
  • Suchánková, Jana
  • Batovský, Marian
  • Páv, Igor
http://linked.open...ain/vavai/riv/wos
  • 000308043300021
issn
  • 0163-2116
number of pages
http://bibframe.org/vocab/doi
  • 10.1007/s10620-012-2163-y
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  • 16370
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