Genetic polymorphism of thiopurine S-methyltransferase: Molecular mechanisms and clinical importance

Citation
Ey. Krynetski et We. Evans, Genetic polymorphism of thiopurine S-methyltransferase: Molecular mechanisms and clinical importance, PHARMACOL, 61(3), 2000, pp. 136-146
Citations number
70
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOLOGY
ISSN journal
00317012 → ACNP
Volume
61
Issue
3
Year of publication
2000
Pages
136 - 146
Database
ISI
SICI code
0031-7012(2000)61:3<136:GPOTSM>2.0.ZU;2-U
Abstract
The activity of thiopurine S-methyltransferase (TPMT) is inherited as an au tosomal co-dominant trait. In most large world populations studied to date, approximately 10% of the population have intermediate activity due to hete rozygosity at the TPMT locus, and about 0.33% is TPMT deficient, TPMT is no w one of the most well characterized genetic polymorphisms of drug metaboli sm, with the genetic basis having been well defined in most populations, pr oviding molecular strategies for studying this genetic polymorphism in huma n and experimental models. Three mutant alleles, TPMT*2, TPMT*3A and TPMT*3 C, account for the great majority of mutant alleles in all human population s studied to date. Significant ethnic differences occur in the frequencies of these mutant alleles, Progress in DNA analysis has made it practical to use genotyping techniques for the molecular diagnosis of TPMT deficiency an d heterozygosity, thereby avoiding adverse effects that are more prevalent in TPMT-deficient and heterozygous patients prescribed thiopurine medicatio ns. Copyright(C)2000S.KargerAG,Basel.