Thiopurine methyltransferase alleles in British and Ghanaian populations

M M Ameyaw, E S R Collie-Duguid, R H Powrie, D Ofori-Adjei, H L McLeod

Research output: Contribution to journalArticle

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Abstract

Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 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.

Original languageEnglish
Pages (from-to)367-370
Number of pages4
JournalHuman Molecular Genetics
Volume8
Publication statusPublished - 1999

Keywords

  • ACUTE LYMPHOBLASTIC-LEUKEMIA
  • S-METHYLTRANSFERASE
  • MERCAPTOPURINE METABOLISM
  • GENETIC-POLYMORPHISM
  • CATALYTIC ACTIVITY
  • BLACK SUBJECTS
  • PHARMACOGENETICS
  • DEFICIENCY
  • 6-MERCAPTOPURINE
  • AZATHIOPRINE

Cite this

Ameyaw, M. M., Collie-Duguid, E. S. R., Powrie, R. H., Ofori-Adjei, D., & McLeod, H. L. (1999). Thiopurine methyltransferase alleles in British and Ghanaian populations. Human Molecular Genetics, 8, 367-370.

Thiopurine methyltransferase alleles in British and Ghanaian populations. / Ameyaw, M M ; Collie-Duguid, E S R ; Powrie, R H ; Ofori-Adjei, D ; McLeod, H L .

In: Human Molecular Genetics, Vol. 8, 1999, p. 367-370.

Research output: Contribution to journalArticle

Ameyaw, MM, Collie-Duguid, ESR, Powrie, RH, Ofori-Adjei, D & McLeod, HL 1999, 'Thiopurine methyltransferase alleles in British and Ghanaian populations', Human Molecular Genetics, vol. 8, pp. 367-370.
Ameyaw, M M ; Collie-Duguid, E S R ; Powrie, R H ; Ofori-Adjei, D ; McLeod, H L . / Thiopurine methyltransferase alleles in British and Ghanaian populations. In: Human Molecular Genetics. 1999 ; Vol. 8. pp. 367-370.
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abstract = "Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 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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T1 - Thiopurine methyltransferase alleles in British and Ghanaian populations

AU - Ameyaw, M M

AU - Collie-Duguid, E S R

AU - Powrie, R H

AU - Ofori-Adjei, D

AU - McLeod, H L

PY - 1999

Y1 - 1999

N2 - Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 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.

AB - Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 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.

KW - ACUTE LYMPHOBLASTIC-LEUKEMIA

KW - S-METHYLTRANSFERASE

KW - MERCAPTOPURINE METABOLISM

KW - GENETIC-POLYMORPHISM

KW - CATALYTIC ACTIVITY

KW - BLACK SUBJECTS

KW - PHARMACOGENETICS

KW - DEFICIENCY

KW - 6-MERCAPTOPURINE

KW - AZATHIOPRINE

M3 - Article

VL - 8

SP - 367

EP - 370

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

ER -