Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S -methyltransferase (TPMT) has been estab-lished for Caucasians, but itremains to be elucidated in African populations. In the current study, wedetermined TPMT genotypes in a population of 248 African-Americans andcompared it with allele frequencies in 282 Caucasian Americans. TPMTgenotype was determined in all individuals with TPMT activity indicative ofa heterozygous genotype (10.2 U/ml pRBC, n = 23African-Americans, n = 21 Caucasians). No mutant alleles were found in thehigh activity control groups. The overall mutant allele frequencies weresimilar in African-Americans and Caucasians (4.6 and 3.7% of alleles,respectively). However, while TPMT*3C was the most prevalent mutant allelein African-Americans (52.2% of mutant alleles), it represented only 4.8% ofmutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A andTPMT*2 were less common in African-Americans (17.4 and 8.7% of mutantalleles), whereas TPMT*3A was the most prevalent mutant allele inCaucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containinga single nucleotide transition (G644A), leading to an amino acid change atcodon 215 (Arg-->His), was found in one African-American withintermediate activity. These data indicate that the same TPMT mutantalleles are found in American black and white populations, but that thepredominant mutant alleles differ in these two ethnic groups.