Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms
Journal of the Neurological Sciences Feb 20, 2020
Lorenzoni PJ, et al. - Researchers investigated myasthenia gravis (MG) patients for the prevalence of thiopurine S-methyl-transferase (TPMT) genotypes and their association with adverse events due to azathioprine therapy. The prevalence of the most common TPMT genotypes (*2, *3A, *3B and *3C) was investigated in 50 MG patients from Southern Brazilian using allele-specific polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP) analysis. TPMT gene variants were prevalent in 12%. Variant TPMT*2 (C238G), TPMT*3A (G460A/A719G), TPMT*3B (G460A), and TPMT*3C (A719G) genotypes had the allelic frequency of 1%, 3%, 2% and 1%, respectively. In 44% of MG patients, adverse reactions due to azathioprine therapy occurred; of these, 86% were minor and 14% were major. Compared with other Brazilian populations, they identified the different profiles of TPMT genotypes. In contrast to expectation, they observed different Hardy-Weinberg equilibrium and allelic frequencies of TPMT*3A and TPMT*3B, respectively, a finding that infers a possible founder effect. For TPMT genotypes vs wild-type, statistically significant major adverse events were observed. Despite an association of TPMT genotype with Azathioprine (AZA)-related adverse events, there was no statistically significant difference among wild-type and other TPMT genotypes for minor adverse events, supporting the view that TPMT genotype alone is not sufficient to appropriately personalize the AZA therapy in MG patients. These outcomes are significant for characterizing the prevalence of TPMT gene variants in MG patients managed with AZA and associate the adverse events of this therapy in a real-world outpatient clinic from Southern Brazil.
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