Thiopurine S-methyltransferase (TPMT) activity cutoffs in the Thai population

Abstract

BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT activity ranges and identified clinically applicable thresholds to distinguish individuals with normal TPMT function from those with reduced or deficient activity.MethodsA total of 457 participants, including 207 children and 250 healthy adults without prior thiopurine drug exposure, were enrolled. TPMT activity was measured and common defective genetic variants (TPMT*3A, TPMT*3B, and TPMT*3C) were detected. To determine TPMT activity cutoff values and maximize sensitivity and specificity, receiver operating characteristic curve analysis was employed.ResultsThe cutoff values for TPMT activity in children were ≥52.9 nmol 6-MMP/g Hb/h for persons of the wild type and <52.9 nmol 6-MMP/g Hb/h for individuals who were heterozygous. In adults, the cutoff values were ≥44.6, 31.58-44.5, and <31.58 nmol 6-MMP/g Hb/h for wild-type, heterozygous, and compound heterozygous individuals, respectively. The sensitivity and specificity were 79.29% and 100% in children, whereas, in adults, they were 61.86% and 78.57%, 38.46% and 64.73%, and 100% and 95.98% in the wild-type, heterozygous, and compound heterozygous, respectively.ConclusionsIdentifying TPMT activity cutoff values is crucial for managing patients receiving thiopurine therapy, especially in Thailand. This approach allows for personalized treatment plans and minimizes the risk of adverse drug reactions. Since TPMT activity cutoff values can differ by population and testing methods, it is important to establish specific cutoff values locally.

Keywords: 6-mercaptopurine; Pharmacogenomics; ROC curve; adult; child; cutoff; drug-related side effects and adverse reactions; precision medicine; thiopurine methyltransferase.