Adverse reactions to azathioprine cannot be predicted by thiopurine S-methyltransferase
genotype in Japanese patients with inflammatory bowel disease.
 Human genes: TPMT, thiopurine S-methyltransferase
; PACSIN2, protein kinase C and casein kinase substrate in neurons 2; GSTM1, glutathione S-transferase mu 1.
A genetic deficiency in an enzyme which converts 6-mercaptopurine (Thiopurine S-Methyltransferase
) as well as polymorphisms in genes for several other components of the same metabolic pathway can lead to hematologic and liver toxicities.
There is no doubt that the thiopurine S-methyltransferase
(TPMT) gene polymorphism is one of them.
They are cytochrome P450 2D6 and thiopurine S-methyltransferase
Genetic polymorphism of thiopurine S-methyltransferase
: clinical importance and molecular mechanisms.
Molecular diagnosis of thiopurine S-methyltransferase
deficiency: genetic basis for azathioprine and mercaptopurine intolerance.
In a report recently published in this journal (1), Reinshagen et al., who investigated 6-thioguanine nucleotide (6-TGN) concentrations in patients with inflammatory bowel disease (IBD), concluded that standard and adapted dosing of azathioprine led to identical 6-TGN concentrations and remission rates and that therapeutic drug monitoring of thiopurine therapy was of no clinical benefit in patients with a wild-type thiopurine S-methyltransferase
The thiopurine S-methyltransferase
gene locus--implications for clinical pharmacogenomics.
First, there is now a commercially available diagnostic test measuring a patient's ability to produce the metabolic enzyme thiopurine S-methyltransferase
(TPMT), which is essential for the metabolism of thiopurine medications used to treat acute lymphoblastic leukemia (ALL), the most common form of childhood cancer.
: a genetic polymorphism that affects a small number of drugs in a big way.
Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase
deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study.