Genotype and Phenotype Correlation of the TPMT∗8 Allele in Thiopurine Metabolism.

Thiopurine 6-mercaptopurine (6-MP) is metabolized by thiopurine methyl transferase (TPMT). TPMT genetic variation results in some individuals having reduced or absent TPMT enzyme activity. If these individuals take a full thiopurine dose, life-threatening adverse events can occur. Testing identifies patients with reduced or absent TPMT activity and is recommended before initiation of therapy. The TPMT∗8 allele, defined by c.644G>A (p.Arg215His), is common among individuals of African ancestry (approximately 2.3% minor allele frequency) but is not included in genotyping recommendations due to its uncertain function. Here, a clinical TPMT enzyme activity assay was used to assess TPMT activity in red blood cells from 982 patients, including those with ∗1/∗8 (n = 22), ∗3A/∗8 (n = 1), and ∗3C/∗8 (n = 1) TPMT diplotypes. The average production of 6-methylmercaptopurine (primary TPMT product measured clinically) was 3.08 ± 0.16 nmol/mL per hour for ∗1/∗8 individuals, compared with 3.77 ± 0.03 nmol/mL per hour for normal metabolizers (P = 0.0001) and 2.39 ± 0.06 nmol 6-methylmercaptopurine/mL per hour for intermediate metabolizers (P < 0.0001). Individuals with a TPMT∗1/∗8 diplotype displayed reduced 6-MP metabolism between that of normal metabolizers and intermediate metabolizers, suggesting that TPMT∗8 is a reduced function allele.

Sterner RM ，Hall PL ，Matern D ，Black JL ，Moyer AM ... -  《-》

Validation of a high-performance liquid chromatography method for thiopurine S-methyltransferase activity in whole blood using 6-mercaptopurine as substrate.

Rieger H ，Schmidt P ，Schaeffeler E ，Abe M ，Schiffhauer M ，Schwab M ，von Ahsen N ，Zurek G ，Kirchherr H ，Shipkova M ，Wieland E ... -  《-》

Thiopurine S-methyltransferase phenotype-genotype correlation in children with acute lymphoblastic leukemia.

Chrzanowska M ，Kuehn M ，Januszkiewicz-Lewandowska D ，Kurzawski M ，Droździk M ... -  《ACTA POLONIAE PHARMACEUTICA》

Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed patients.

Chrzanowska M ，Kurzawski M ，Droździk M ，Mazik M ，Oko A ，Czekalski S ... -  《Pharmacological Reports》

Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China).

Zhang LR ，Song DK ，Zhang W ，Zhao J ，Jia LJ ，Xing DL ... -  《CLINICA CHIMICA ACTA》