Thiopurine methyltransferase alleles in British and Ghanaian populations |
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Authors: | Ameyaw MM; Collie-Duguid ES; Powrie RH; Ofori-Adjei D; McLeod HL |
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Institution: | University of Aberdeen, Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. |
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Abstract: | Thiopurine methyltransferase (TPMT) catalyses the S-methylation of
thiopurine drugs such as 6-mercapto-purine, 6-thioguanine and azathioprine.
TPMT activity 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 in different ethnic groups. The frequency of four allelic variants
of the TPMT gene, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were compared in
British Caucasian (n = 199) and Ghanaian (n = 217) populations using
PCR-RFLP and allele- specific PCR-based assays. TPMT*3C was found in 14.8%
of Ghanaians (31 heterozygotes, 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*3A (n = 17) and TPMT*3C (n = 1) alleles. The
frequencies of mutant alleles in this study were 5.3 and 7.6% in British
Caucasians and Ghanaians, respectively. 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 reach 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.
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