Hl. Mcleod et al., Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals, PHARMACOGEN, 9(6), 1999, pp. 773-776
Thiopurine methyltransferase (TPMT) degrades 6-mercaptopurine, azathioprine
and 6-thioguanine which are commonly used in the treatment of autoimmune d
iseases, leukaemia and organ transplantation, TPMT activity is polymorphic
as a result of gene mutations. Heterozygous individuals have an increased r
isk of haematological toxicity after thiopurine medication, while homozygou
s mutant individuals suffer life threatening complications. Previous popula
tion studies have identified ethnic variations in both phenotype and genoty
pe, but limited information is available within African populations. This s
tudy determined the frequency of common TPMT variant alleles in 101 Kenyan
individuals and 199 Caucasians, The frequency of mutant alleles was similar
between the Caucasian (10.1%) and Kenyan (10.9%) populations, However, all
mutant alleles br the Kenyan population were TPMT*3C compared with 4.8% in
Caucasians, in contrast TPMT*3A was the most common mutant allele in the C
aucasian individuals. This study confirms ethnic differences in the predomi
nant mutant TPMT allele and the findings will be useful for the development
of polymerase chain reaction-based strategies to prevent toxicity with thi
opurine medications. Pharmacogenetics 9:773-776 (C) 1999 Lippincott William
s & Wilkins.