Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms

Krynetski, Eugene Y.; Tai, Hung‐Liang; Yates, Charles R.; Fessing, Michael Y.; Loennechen, Thrina; Schuetz, John D.; Relling, Mary V.; Evans, William E.

doi:10.1097/00008571-199608000-00001

Cited by 240 publications

(128 citation statements)

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“…Consequently, we studied TPMT and ITPA allele frequencies and investigated the association between the resulting genotypes and thiopurine toxicity in 262 IBD patients established on AZA [37]. TPMT allele frequencies found in our cohort of IBD patients were very similar to those reported in other Caucasian populations [31,38,39]: 238 (90.8%) patients carried wild-type alleles, 17 (6.5%) and 6 (2.2%) proved heterozygous for TPMT*3A and TPMT*3C respectively and 1 (0.4%) patient was a homozygous TPMT *3A mutant. ITPA allele frequencies in our population however, were higher than reported in other populations [40,41]: 173 (66.0%) patients carried wild-type alleles, 29 (11.1%) and 55 (21.0%) patients were heterozygous mutants for C94A and IVS2+A21C respectively and 1 (0.4%) and 4 (1.5%) homozygous mutants for C94A and IVS2+A21C respectively were identified.…”

Section: Genotypingsupporting

confidence: 61%

“…The reported frequency of the leukopenia may be as high as 11%, depending on the definition of leukopenia and the dose prescribed [37]. Type B reactions (2%) often occur within three to four weeks after start of treatment and result in immune-mediated symptoms like fever, rash and arthralgia [38,39]. Also, pancreatitis (1.4-3.3%) is thought to be an idiosyncratic reaction [6,34].…”

Section: Toxicitymentioning

confidence: 99%

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Thiopurines in inflammatory bowel disease: New strategies for optimization of pharmacotherapy?

Derijks

Hommes²

2006

Curr Gastroenterol Rep

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Section: Genotypingsupporting

confidence: 61%

Section: Toxicitymentioning

confidence: 99%

Thiopurines in inflammatory bowel disease: New strategies for optimization of pharmacotherapy?

Derijks

Hommes²

2006

Curr Gastroenterol Rep

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“…1.1.67) activity. TPMTis a cytosolic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including the anticancer agents mercaptopurine and thioguanine and the immunosuppressant AZA (1). TPMTactivity shows codominant genetic polymorphism (2,3).…”

Section: Introductionmentioning

confidence: 99%

Thiopurine Methyltransferase Genotype and the Toxicity of Azathioprine in Japanese.

et al. 1999

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Objective Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including Azathioprine (AZA). It has been reported that the level ofAZA toxicity is dependent on the TPMT genotypes in Caucasian individuals; we thus investigated this relationship in Japanese. Methods The TPMTgenotype was determined using peripheral blood cell DNAobtained from 36 Japanese patients with rheumatic diseases who were treated with AZA,by polymerase chain reaction (PCR) technique. Duration ofAZAadministration, white blood cell counts before and after AZAadministration, and side effects were investigated in each subject, and were compared between the patients with or without TPMTmutation. Results The TPMTallelotype was TPMT*1ITPMT*1 in 33 (91.7%) and TPMT*1/TPMT*3Cin 3 (8.3%) individuals.All 3 patients (100%) with the mutant TPMTallele (TPMT*3C) discontinued AZAtreatment due to leucopenia while only 4 patients (12%) without mutant TPMTalleles showed leucopenia (p=0.0049, Fisher's exact test). However, leucopenia developed relatively late in patients with mutant TPMT. Conclusion The TPMTmutant allele, TPMT*3C,also exists in Japanese individuals, and the bone marrow toxicity of AZAis likely stronger in patients with this mutant allele. (Internal Medicine 38: 944-947, 1999)

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“…Около 10 % людей имеют сниженную активность ТРМТ и в 0,3% случаев активность фермента не определяется [27,28].…”

Section: заключениеunclassified

Clinical significance of polymorphism of thiopurine methyltransferase gene in children with acute lymphoblastic leukemia during programmed therapy

Петина¹,

Зборовская²,

Матевосян³

et al. 2017

Ross. ž. det. gematol. onkol.

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Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms

Cited by 240 publications

References 0 publications

Thiopurines in inflammatory bowel disease: New strategies for optimization of pharmacotherapy?

Thiopurines in inflammatory bowel disease: New strategies for optimization of pharmacotherapy?

Thiopurine Methyltransferase Genotype and the Toxicity of Azathioprine in Japanese.

Clinical significance of polymorphism of thiopurine methyltransferase gene in children with acute lymphoblastic leukemia during programmed therapy

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