Thiopurine methyltransferase as a therapeutic indicator of purine analogues: a preliminary study in southern metropolis

Sadik A. M.*, Siva Prasad S., Guru Prasad M., Sasikala M., Manu Tandon, Rupa Benerjee, Nageshwar Reddy D.

Abstract


The purine analogues used to treat certain chronic diseases are occasionally associated with bone marrow suppression and leucopenia. They are metabolized by Thiopurine S-methyltransferase (TPMT) to methyl mercaptopurines. Thus optimal TPMT activity of an individual plays an important role in the treatment. However a wide interindividual variation of TPMT activity may be multi-factorial including inter and intra familial genotypic variation of TPMT gene. The present study was aimed to establish the reference range of TPMT activity and correlated with genotype.  165 healthy blood donors (Male-133. Female-32) were assessed for their TPMT activity by HPLC-UV method. The mean age of study cohort was 30.4±8.7 (19-58) and 150 of them were analyzed for TPMT *2, *3B and *3C polymorphisms by PCR-direct sequencing. The range of TPMT activity was found to be wide (3.93 to 35.80 nmolml-1h-1PRBC). The mean of the TPMT activity in total population was 15.98± 7.95, in females 10.99±3.44 and in males it is 15.19±7.64. All the participants studied for TPMT gene polymorphism were found to be wild type for all major polymorphic regions. The range of TPMT activity has a wide range. The wide reference range of enzyme activity may have multi-factorial basis. The frequency of hetero and homozygous variants of screened polymorphisms in TPMT gene may be less frequent in South Indian population.

Keywords


Thiopurine S-methyltransferase; Thiopurine drugs; HPLC

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DOI: http://dx.doi.org/10.21746/ijbio.2013.10.0015

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