Thiopurine methyltransferase phenotypes and genotypes in Brazilians.

The polymorphism of thiopurine methyltransferase (TPMT) was studied in 306 healthy Brazilians who were classed, on the basis of self-declared colour and ancestry, as Euro-derived (n = 81), Afro-derived (n = 18) or having interethnic admixture (n = 204). TPMT activity (range 0.17-25.93 U) displayed a trimodal distribution of high (> 11.3 U; 9% of individuals), intermediate (5-11.3 U; 9.8%) and low (0.17 U; 0.3%) phenotypes. The occurrence of the TPMT mutations 238G>C, 460G>A and 719A>G was investigated in all individuals with low or intermediate phenotype, and in 43 with high-activity phenotype. None and two mutant alleles were associated with high- or low-activity phenotypes, respectively, whereas one mutant allele was detected in 26 of the 30 intermediate phenotype individuals. The allele frequencies of TPMT2, TPMT3A and TPMT3C did not differ between individuals classed as Euro-derived (0.76%, 2.03% and 2.54%, respectively) or having interethnic admixture (0.60%, 1.81% and 1.81%, respectively). Furthermore, within each of these groups, the frequencies of TPMT3A and TPMT*3C were not significantly different.