Abstract:
INTRODUCTION:Thiopurine drugs are metabolized via S-methylation and catalyzed by thiopurine S-methyltransferase (TPMT). Patients with very low TPMT activity are at high risk of fatal bone marrow toxicity when standard doses of thiopurine drugs are administered. TPMT genotyping can predict TPMT activity and is not affected by transfusion or red blood cell defects. Here, we report a new allele-specific real-time polymerase chain reaction (PCR) system for thiopurine methyltransferase genotyping that is validated in Korean population. MATERIALS AND METHODS:Three major TPMT single-nucleotide polymorphisms (TPMT 2, 3B, and 3C) were genotyped using real-time PCR with the allele-specific primers and probes. Internal positive controls were included in each well, and an automatic interpretative algorithm was applied. This system was validated using 244 clinical samples and 2 commercial DNA samples that had been previously genotyped using PCR-direct sequencing. Results. All of the obtained results are concordant with those of the reference method. All of the internal positive control reactions were successful. The allele frequency of TPMT 3C was 2.05% (10 of 488 alleles). All of the patients with variant alleles were heterozygotes, and no homozygotes were detected. No TPMT 2, 3A, or 3B alleles were observed in this Korean population. CONCLUSION:This rapid, accurate, and user-friendly genotyping system can be readily used to improve the efficacy and safety of thiopurine treatments in clinical practice.
journal_name
Biomed Res Intjournal_title
BioMed research internationalauthors
Kim S,Lee HW,Lee W,Chun S,Min WKdoi
10.1155/2013/305704subject
Has Abstractpub_date
2013-01-01 00:00:00pages
305704eissn
2314-6133issn
2314-6141journal_volume
2013pub_type
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