ALLELE FREQUENCY OF THIOPURINE S-METHYLTRANSFERASE (TPMT) IN HONG KONG POPULATION

Aim Azathioprine, 6-Mercaptopurine and 6-Thioguanine are commonly used in the management of acute leukemia, autoimmune diseases and as the immunosuppressants in organ transplantation. These drugs belong to the class of thiopurine which can inhibit DNA synthesis and cell proliferation of fast growing lymphocytes by suppressing de novo purine synthesis. Thioguanine nucleotides (TGNs) are the active metabolites in which accumulation of high level cytotoxic TGNs can lead to myelosuppression. It has been demonstrated that Thiopurine S-methyltransferase (TPMT) is the key enzyme responsible for catalytic conversion of TGNs to non-cytotoxic methyl-thioguanine. The TPMT gene is polymorphic and TPMT protein variants with reduced enzyme activity are associated with inefficient removal of TGNs. In this study, we aim to investigate the allele frequency of the most common TPMT variants (TPMT*2 and *3C) in Hong Kong population. Methods Genomic DNA from whole blood was extracted. The presence of TPMT*2 and *3C mutant alleles were determined using Amplification-Refractory Mutation System (ARMS) PCR method. Beta-2-microglobulin was used as the internal control. All mutant alleles were confirmed by Sanger’s sequencing. Hong Kong healthy individuals (n = 300) were included in this study. Rare TPMT alleles were not determined. Results TPMT*1/3C genotype was detected in 9 out of 300 healthy subjects while TPMT*2 allele was absent. The allele frequency of TPMT*3C in Hong Kong population is 1.5%. Conclusions This study provides the first analysis of the allele frequency of TPMT variants in Hong Kong population and our finding is in accordance with the reported frequency range in Chinese population. TPMT*3C is the most common TPMT variant in Hong Kong subjects. The establishment of TPMT genotyping assay for patient requires thiopurine therapy will provide additional information to guide the reduction of drug dose to minimize the risk of myelosuppression.