Genomic structure and multiple single-nucleotide polymorphisms (SNPs) of the thiopurine S-methyltransferase (TPMT) gene.

Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of drugs such as azathiopurine, 6-mercaptopurine, and 6-thioguanine, which are widely prescribed for immunosuppressive or cytotoxic applications. We report here the entire genomic structure of the TPMT gene and the presence of 30 single-nucleotide polymorphisms (SNPs) within that structure. The gene spans a genomic region about 27kb long and consists of nine exons. By screening its entire genomic sequence for SNPs in 48 Japanese chromosomes by direct DNA sequencing, we detected 1 SNP in the 870-bp promoter region, 26 SNPs in introns, and 3 SNPs in the 3' untranslated region (3'UTR) for investigating correlations between TPMT genotypes and the side-effects caused by thiopurine drugs.