کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1967851 1538752 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China)
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China)
چکیده انگلیسی

BackgroundThiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined.MethodsIn 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT⁎2, ⁎3A, ⁎3B and ⁎3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population.ResultsSeven TPMT⁎3C heterozygotes were identified, while TPMT⁎2, ⁎3A and ⁎3B alleles were not detected in 248 healthy subjects. The frequency of TPMT⁎3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03 ± 4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis.ConclusionsWe defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 376, Issues 1–2, 1 February 2007, Pages 45–51
نویسندگان
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