Frequency of thiopurine S-methyltransferase genetic variation in Thai children with acute leukemia

Abstract

Background. Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation (inactivation) of mercaptopurine, azathioprine, and thioguanine, and exhibits genetic variation. About 11% of Caucasians have intermediate TPMT activity because of heterozygosity, and about 1 in 300 inherits TPMT deficiency as an autosomal codominant trait. If patients who have intermediate or deficient TPMT activity receive the standard dose of thiopurine medications, they can accumulate excessive thiopurine nucleotides in hematopoietic tissue, which could lead to severe and possibly fatal myelosuppression. There is very little information about TPMT genetic variation among Asian populations. We investigated the frequency of TPMT genetic variation among Thai children with acute leukemia. Procedure. Fresh whole blood was obtained from 75 Thai children with acute leukemia at the time of remission. Genomic DNA was isolated from total peripheral white blood cells. We performed polymerase chain reaction (PCR) to detect 3 types of variant of the human TPMT gene. Results. Among 75 patients, the frequency of heterozygotes for the TPMT gene among Thai children with acute leukemia was ~11%. However, the TPMT(*)3C was the only variant TPMT allele found among Thai children. This is different from the North American Caucasian populations, in which TPMT(*)3A is the predominant variant allele, and TPMT(*)3C is rare (~5% of variant alleles). Conclusions. There is no difference in the frequency of this genetic variation between Asian and North American Caucasian populations. Determination of the TPMT genotype by PCR method before antileukemic therapy is practical and may have clinical relevance. This knowledge could be applied towards organ transplant recipients who require these medications for immunosuppression. (C) 2000 Wiley-Liss, Inc.