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

The molecular basis for the genetic polymorphism of thiopurine S-methyltran sferase (TPMT) has been established for Caucasians, but it remains to be el ucidated in African populations. In the current study, we determined TPMT g enotypes in a population of 248 African-Americans and compared it with alle le frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (l ess than or equal to 10.1 U/ml pRBC, n = 23 African-Americans, n = 21 Cauca sians) and a control group with TPMT activity indicative of a homozygous wi ld-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasi ans), No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Ca ucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C wa s the most prevalent mutant allele in African-Americans (52.2% of mutant al leles), it represented only 4.8% of mutant alleles in Caucasians (P < 0.001 ), In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (1 7.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mut ant allele in Caucasians (85.7% of mutant alleles), A novel allele(TPMT*8), containing a single nucleotide transition (G844A), leading to an amino aci d change at codon 215 (Arg-->His), was found in one African-American with i ntermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominan t mutant alleles differ in these two ethnic groups.