gb PHARM TPMT

• kit requires manual preparation of reagents and samples, which are then analysed with the use of real-time PCR cycler instrument
• intended for testing in Caucasian population
• intended for laboratory professional use by trained healthcare professionals
• detection of rs1800462, rs1800460 and rs1142345 polymorphisms serves as an aid to identify patients at risk of adverse events when using thiopurine drugs
• kit allows the determination of haplotypes TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C in homozygous or heterozygous form
• kit does not distinguish genotype *1/*3A (two mutations in cis form) from 3B*/*3C (the incidence of the composite heterozygote *3B/3C* is unlikely in Caucasians)

Clinical implications

Thiopurine S-methyltransferase (TPMT) is an essential enzyme for biodegradation of thiopurines. Antitumor drugs thioguanine and mercaptopurine, related to thiopurines, are used especially in hematooncology. Another thiopurine, azathioprine, is an immunosuppressive agent intended for the treatment of autoimmune diseases and prevention of transplant rejection. The thiopurine drug side effects include neurotoxicity, hepatotoxicity, myelosuppression, mucositis and others. The biotransformation activity of the TPMT enzyme may be reduced due to the presence of the single nucleotide polymorphisms in the coding region of the TPMT gene. The most studied deficient alleles are TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. Limited thiopurine biotransformation leads to the escalation of side effects of treatment. Upon detection of heterozygote it is recommended to reduce the dose of the drug to 30-70%, in the case of the homozygote and the composite heterozygote it is better to choose an alternative treatment.