%0 Generic %A Gong, Xiaoqing %A Mei, Shenghui %A Li, Xindi %A Li, Xingang %A Zhou, Heng %A Liu, Yonghong %A Zhou, Anna %A Yang, Li %A Zhao, Zhigang %A Zhang, Xinghu %D 2017 %T Association between TPMT*3C and decreased thiopurine S-methyltransferase activity in patients with neuromyelitis optica spectrum disorders in China %U https://tandf.figshare.com/articles/dataset/Association_between_TPMT_i_i_3C_and_decreased_thiopurine_S-methyltransferase_activity_in_patients_with_neuromyelitis_optica_spectrum_disorders_in_China/5657308 %R 10.6084/m9.figshare.5657308.v1 %2 https://ndownloader.figshare.com/files/9869263 %K Thiopurine S-methyltransferase activity %K neuromyelitis optica spectrum disorders %K TPMT*3C %K rs1142345 %K genetic polymorphisms %X

Aim of the study: 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*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.

Material and methods: 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.

Results: 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*3C (rs1142345) was associated with lower thiopurine S-methyltransferase activity (BETA = −25.37, P = 0.011). Other selected variants were not associated with thiopurine S-methyltransferase activity.

Conclusions: TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results.

Abbreviations:TPRs = thiopurines; NMOSD = neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase; LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6-methylmercaptopurine; IS = internal standard; SNP = single nucleotide polymorphism; MAF = minor allele frequency; HWE = Hardy–Weinberg equilibrium; BETA = regression coefficients; UTR-3 = untranslated region 3

%I Taylor & Francis