Methylated and Non Methylated Thiopurine Nucleotide Ratio (ME6-MPN/6-TGN): Usefulness in the Monitoring of Azathioprine Therapy?

TL;DRAbstract

Azathioprine is routinely coadministered with cyclosporine and corticoides to prevent rejection episodes after transplantation. Immunosuppressive and myelotoxic effects of azathioprine are considered to be related to metabolic conversion to thiopurine metabolites. In red blood cells, two different metabolic pathways are in competition, one leading to non methylated 6-thiopurine nucleotides essentially 6-thioguanine nucleotides (6-TGN), another leading to methylated 6-thiopurine nucleotides principally methyl 6-mercaptopurine nucleotides (Me6-MPN) via thiopurine methyl transferase (TPMT) 1,2 . The activity of TPMT in red blood cells exhibits genetic polymorphism, with approximately 1 in 300 subjects who inherit TPMT deficiency as an autosomal recessive trait, and about 89% of caucasians are homozygous for the high activity alleles3. Low TPMT activity has been related 3,4 to severe myelosuppression associated with high

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