TPMT Mutation Detection with Single Nucleotide Sequencing
Thiopurine drugs such as azotioprin (AZA), 6-merkaptopurine (6-MP) and 6-thioguanine (6-TG) are widely used in treatment of Acute Lymphoblastic Leucemia (ALL), autoimmune diseases, inflammatory bowel disease and posttransplant organ treatment. In the patients with high thipurine methyltransferase enzyme activity due to genetic factors and/or drug-drug interaction, there is a high risk of toxicity when thiopurine drugs are administered. TPMT enzyme deficiency is an autosomal dominant disease.
Molecular genetic basis of TPMT polymorphism is not well known. To date, more than 10 allelic variants of TPMT has reported. In the patients with a decrease in TPMT activity, three main TPMT variants (TPMT-3A, TPMT-3B, TPMT-3C) are observed. These variant alleles caused by point mutations on exons or mutations on intron-exon boundaries.