Genetic determinants of the pre- and post-azathioprine therapy thiopurine methyltransferase activity phenotype.
Thiopurine drug therapy has been reported to lead to a variable increase in red cell TPMT activity that may alter effective dose and therapeutic outcome. The aim of this study was to correlate Variable Number Tandem Repeat (VNTR) in the promoter region of the TPMT gene with induction of red cell TPMT activity in patients treated with azathioprine (AZA). In 58 patients, TPMT activity measured at 3 months was not significantly induced on average above pre-therapy levels. Individual patients showed variation in TPMT activity pre- and post-AZA therapy, however changes in TPMT activity were not predicted by VNTR configuration. In conclusion, TPMT promoter VNTRs are unlikely to play a significant role in changes in TPMT activity in response to AZA therapy.
Arenas
M
M
Purine Research, Guy's and St. Thomas' Hospital, London, UK.
Duley
J A
JA
Ansari
A
A
Shobowale-Bakre
E A
EA
Fairbanks
L
L
Soon
S Y
SY
Sanderson
J
J
Marinaki
A M
AM
D000483:Alleles; D000963:Antimetabolites / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D004912:Erythrocytes / Q000201:enzymology; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D018598:Minisatellite Repeats; D016366:Open Reading Frames; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011687:Purines / Q000737:chemistry; D013997:Time Factors
D000963:Antimetabolites; D011687:Purines; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine