کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1969546 1059775 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients
چکیده انگلیسی

Background and aimsTPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). However, in one previous study, only about ¼ of MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT deficiency. Recently, new TPMT mutations have been described and our aim is to investigate their clinical relevance before and after a first MS episode on thiopurine therapy.MethodsClinical data from 61 IBD patients having developed MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT cDNA for the presence of all currently known mutations.ResultsOnly TPMT *2, *3A and *3C mutations were found in this cohort. TPMT mutations were observed in 15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator, IM genotype). Median delays of MS onset were 2, 2.75 and 6 months in the LM, IM and HM (high methylator, wild type TPMT) groups, respectively. After the first MS episode, 36 patients resumed thiopurine treatment of which 13 experienced a second MS episode. This second episode was also rarely associated with TPMT mutations.ConclusionsOne quarter of MS episodes during AZA were associated with TPMT deficient genotype. After a first leucopenia episode, thiopurine therapy may be resumed in a majority of patients independently of their TPMT genotype.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Biochemistry - Volume 44, Issue 13, September 2011, Pages 1062–1066
نویسندگان
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