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Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms.
Lorenzoni, Paulo José; Kay, Cláudia Suemi Kamoi; Zanlorenzi, Marcelo Farago; Ducci, Renata Dal-Prá; Werneck, Lineu Cesar; Scola, Rosana Herminia.
Afiliação
  • Lorenzoni PJ; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil. Electronic address: lorenzoni@ufpr.br.
  • Kay CSK; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
  • Zanlorenzi MF; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
  • Ducci RD; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
  • Werneck LC; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
  • Scola RH; Service of Neuromuscular Disorders, Division of Neurology, Department of Internal Medicine, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, Brazil.
J Neurol Sci ; 412: 116734, 2020 May 15.
Article em En | MEDLINE | ID: mdl-32070863
Azathioprine (AZA) is the most common immunosuppressive drug used to treat myasthenia gravis (MG). To analyses the prevalence of thiopurine S-methyl-transferase (TPMT) genotypes and their association with adverse events due to azathioprine therapy in MG patients. Allele-specific polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP) analysis were carried out to determine the prevalence of the most common TPMT genotypes (*2, *3A, *3B and *3C) in 50 MG patients from Southern Brazilian. The frequency of adverse reactions due to azathioprine therapy was analysed and correlated with different genotypes groups. The prevalence of TPMT gene variants was 12%. The allelic frequency of variant TPMT*2 (C238G), TPMT*3A (G460A/A719G), TPMT*3B (G460A), and TPMT*3C (A719G) genotypes was 1, 3, 2 and 1%, respectively. Adverse events occurred in 44%, of MG patients, of which 86% were minor and 14% were major. One patient, who presented a major adverse event (bone marrow suppression), was homozygous for the TPMT*3A genotype. Our study estimated the prevalence of TPMT genotypes for Brazilian MG patients. The profile of TPMT genotypes was different from other Brazilian populations. Hardy-Weinberg equilibrium and allelic frequencies of TPMT*3A and TPMT*3B, respectively, were different than expected, a finding that suggests a possible founder effect. Major adverse events were statistically significant for TPMT genotypes compared to wild-type. Although TPMT genotype has been associated with AZA-related adverse events, since no statistically significant difference among wild-type and other TPMT genotypes for minor adverse events, our study supports the view that TPMT genotype alone is not enough to adequately personalise the AZA therapy in MG patients. In conclusion, these results were important to characterise the prevalence of TPMT gene variants in MG patients treated with AZA and correlate the adverse events of this therapy in a real-world outpatient clinic from Southern Brazil.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Azatioprina / Miastenia Gravis Tipo de estudo: Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Sci Ano de publicação: 2020 Tipo de documento: Article País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Azatioprina / Miastenia Gravis Tipo de estudo: Risk_factors_studies Limite: Humans País/Região como assunto: America do sul / Brasil Idioma: En Revista: J Neurol Sci Ano de publicação: 2020 Tipo de documento: Article País de publicação: Holanda