Ey. Krynetski et We. Evans, Genetic polymorphism of thiopurine S-methyltransferase: Molecular mechanisms and clinical importance, PHARMACOL, 61(3), 2000, pp. 136-146
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.