Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals

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.