PMID- 17220558
OWN - NLM
STAT- MEDLINE
DCOM- 20070511
LR  - 20200106
IS  - 1734-1140 (Print)
IS  - 1734-1140 (Linking)
VI  - 58
IP  - 6
DP  - 2006 Nov-Dec
TI  - Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed 
      patients.
PG  - 973-8
AB  - Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme, catalyzing 
      S-methylation of thiopurine drugs. TPMT exhibits autosomal codominant 
      polymorphism. Patients carrying a variant genotype have low TPMT activity, and 
      produce elevated levels of 6-thioguanine nucleotides (6-TGN) in their red blood 
      cells (RBC). 6-TGN accumulation may result in azathioprine (AZA)-induced bone 
      marrow myelosuppression in the course of treatment with the drug in a standard 
      dosage regimen in patients following renal transplantation. In the current study, 
      TPMT activity (phenotype) and genotype were determined in dialyzed patients, 
      qualified for renal transplantation. TPMT activity was measured in RBC after 
      dialysis by HPLC method. Patients were genotyped for TPMT *2, *3A and *3C variant 
      alleles using PCR-RFLP and allele-specific PCR methods. TPMT activity ranged 
      between 12.2 and 45.5 nmol 6-mMP/g Hb/h (median value 30.6). A significant 
      correlation between TPMTphenotype and genotype was noted: the heterozygous 
      patients (11.5%) demonstrated significantly lower mean TPMT activity as compared 
      to the wild homozygotes (17 +/- 3.6 vs. 32.4 +/- 4.8 nmol 6-mMP/g Hb/h, p < 
      0.0003). No overlap in TPMT activity values between the group of heterozygous 
      (range 12.2-20.6) and wild-type homozygous patients (range 22.7-45.5) was noted. 
      TPMT activity, established after hemodialysis and TPMT genotyping results seem to 
      be convergent in dialyzed patients, so both methods can be used for the 
      identification of patients with lower TPMT activity. Such tests could be helpful 
      in AZA dose individualization, and thus in reducing the risk of myelosuppression 
      during AZA therapy following renal transplantation.
FAU - Chrzanowska, Maria
AU  - Chrzanowska M
AD  - Department of Physical Pharmacy and Pharmacokinetics, University of Medical 
      Sciences, Swiecickiego 6, PL 60-781 Poznan, Poland.
FAU - Kurzawski, Mateusz
AU  - Kurzawski M
FAU - Drozdzik, Marek
AU  - Drozdzik M
FAU - Mazik, Marta
AU  - Mazik M
FAU - Oko, Andrzej
AU  - Oko A
FAU - Czekalski, Stanislaw
AU  - Czekalski S
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (azathiopurine)
RN  - E7WED276I5 (Mercaptopurine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Kidney Transplantation
MH  - Male
MH  - Mercaptopurine/analogs & derivatives/metabolism/therapeutic use
MH  - Methyltransferases/*genetics/metabolism
MH  - Middle Aged
MH  - Phenotype
MH  - *Renal Dialysis
EDAT- 2007/01/16 09:00
MHDA- 2007/05/12 09:00
CRDT- 2007/01/16 09:00
PHST- 2006/05/08 00:00 [received]
PHST- 2006/10/18 00:00 [revised]
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2007/05/12 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
PST - ppublish
SO  - Pharmacol Rep. 2006 Nov-Dec;58(6):973-8.