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Further evidence that a variant of the gene NUDT 15 may be an important predictor of azathioprine‐induced toxicity in Chinese subjects: a case report
Author(s) -
Ailing Z.,
Jing Y.,
Jingli L.,
Yun X.,
Xiaojian Z.
Publication year - 2016
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12420
Subject(s) - thiopurine methyltransferase , azathioprine , toxicity , medicine , nephrotoxicity , genotyping , pharmacology , genotype , pharmacogenetics , adverse effect , gastroenterology , gene , genetics , biology , disease
Summary What is known and objective Thiopurine methyltransferase (TPMT) enzyme is an important component in the metabolism of azathioprine ( AZA ). Its mutation may lead to AZA ‐induced toxicity. The dysfunctional genetic variant TPMT *3C is of low frequency among Asians. Moreover, AZA ‐induced toxicity still occurs in some patients with normal TPMT activity. This suggests that additional factors, including other genetic variants, may contribute to such toxicity. Recent studies described a strong association between a variant of the NUDT 15 , a gene that mediates the hydrolysis of some nucleoside diphosphate derivatives, and thiopurine‐related myelosuppression in Asians. We report the first case of a Chinese patient with AZA ‐induced severe toxicity with no clinically significant TPMT variant but with the NUDT 15 c.415C>T allele. Case summary A 40‐year‐old Chinese patient with PBC ‐ AIH overlap syndrome had been receiving for one month, azathioprine (50 mg/day) and methylprednisolone (24 mg/day) based on his TPMT *3C wild‐type genotype. The patient developed serious myelosuppression and hair loss. AZA was stopped, and the patient was given liver‐protective drugs and supportive treatment. TPMT and NUDT 15 gene sequencing suggests that NUDT 15 c.415C>T mutation was the likely cause of the adverse reaction. What is new and conclusion NUDT 15 c.415C>T may be another predictor of AZA ‐induced leukocytopenia. If further well‐controlled studies validate this association with sufficient predictive power, NUDT 15 and TPMT genotyping before starting AZA treatment may become appropriate.