Association between TPMT<i>*</i>3C and decreased thiopurine S-methyltransferase activity in patients with neuromyelitis optica spectrum disorders in China

<b>Aim of the study:</b> Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines’ toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT<i>*</i>3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China. <b>Material and methods:</b> A liquid chromatography tandem mass/mass method was used to evaluate the thiopurine S-methyltransferase activity by using 6-mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by haematocrit and normalized to 8 × 10⁸ erythrocytes. The selected polymorphisms of thiopurine S-methyltransferase were identified using MassARRAY system (Sequenom) and multiple SNaPshot technique. <b>Results:</b> In 69 patients with neuromyelitis optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29–154.53 (127.51 ± 16.83) pmol/h/8 × 10⁸ erythrocytes. TPMT<i>*</i>3C (rs1142345) was associated with lower thiopurine S-methyltransferase activity (BETA = −25.37, <i>P</i> = 0.011). Other selected variants were not associated with thiopurine S-methyltransferase activity. <b>Conclusions:</b> TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results. <b>Abbreviations:</b><i>TPRs</i> = thiopurines; <i>NMOSD</i> = neuromyelitis optica spectrum disorders; <i>TPMT</i> = thiopurine S-methyltransferase; <i>LC-MS/MS</i> = liquid chromatography tandem mass/mass; <i>6-MMP</i> = 6-methylmercaptopurine; <i>IS</i> = internal standard; <i>SNP</i> = single nucleotide polymorphism; <i>MAF</i> = minor allele frequency; <i>HWE</i> = Hardy–Weinberg equilibrium; <i>BETA</i> = regression coefficients; <i>UTR-3</i> = untranslated region 3