Thiopurine methyltransferase alleles in British and Ghanaian populations

Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopuri ne drugs such as 6-mercaptopurine, 6-thioguanine and azathioprine, TPMT act ivity is inherited as an autosomal co-dominant trait, and several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. Although ethnic differences in TPMT activity have been described , population frequency analysis of TPMT alleles has not been well defined i n different ethnic groups. The frequency of four allelic variants of the TP MT gene, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were compared in British Cauc asian (n = 199) and Ghanaian (n = 217) populations using PCR-RFLP and allel e-specific PCR-based assays. TPMT*3C was found in 14.8% of Ghanaians (31 he terozygotes, one homozygote). The TPMT*2, TPMT*3A and TPMT*3B alleles were not detected in any of the Ghanaian samples analysed. In contrast, 10.1% of British subjects had variant alleles, consisting of TPMT*2 (n = 2), TPMT*3 A (n = 17) and TPMT*3C (n = 1) alleles, The frequencies of mutant alleles i n this study were 5.3 and 7.6% in British Caucasians and Ghanaians, respect ively. Among Ghanaian tribes, Ewe subjects had a lower frequency of mutant alleles (5.9%) than Ga (13.2%) or Fanti (11.6%), although this did not reac h statistical significance. This study provides the first analysis of TPMT mutant allele frequency in an African population and indicates that, unlike Caucasians, TPMT*3C is the most common allele in African subjects.