OBJECTIVE: This study was conducted to investigate the thiopurine S-methyltransferase (TPMT) activity distribution and gene mutations in Kazaks, and compared the results with those of other ethnic groups. METHODS: Erythrocyte TPMT activity was measured in Kazaks (n = 327) via a validated high-performance liquid chromatography assay. Polymerase chain reaction-based methods were used to analyze three commonly reporter-inactivating mutations: G238C, G460A, and A719G. RESULTS: Unimodal distribution of TPMT activity was found in Kazaks. Six TPMT*3C heterozygotes and two TPMT*3A heterozygotes were found in 327 Kazaks, with allele frequencies of 0.9 and 0.3%, respectively. The subjects with TPMT*3A and TPMT*3C heterogygotes had substantial TPMT activity over the range of 6.40-11.75 U/ml RBC. CONCLUSION: Unlike in most Caucasians, TPMT*3C is a common mutant allele in Kazaks, whereas TPMT*3A is a rare mutant allele. Further studies are needed to explore the clinical impact of these TPMT mutants to thiopurine therapy in Kazak patients.
OBJECTIVE: This study was conducted to investigate the thiopurine S-methyltransferase (TPMT) activity distribution and gene mutations in Kazaks, and compared the results with those of other ethnic groups. METHODS: Erythrocyte TPMT activity was measured in Kazaks (n = 327) via a validated high-performance liquid chromatography assay. Polymerase chain reaction-based methods were used to analyze three commonly reporter-inactivating mutations: G238C, G460A, and A719G. RESULTS: Unimodal distribution of TPMT activity was found in Kazaks. Six TPMT*3C heterozygotes and two TPMT*3A heterozygotes were found in 327 Kazaks, with allele frequencies of 0.9 and 0.3%, respectively. The subjects with TPMT*3A and TPMT*3C heterogygotes had substantial TPMT activity over the range of 6.40-11.75 U/ml RBC. CONCLUSION: Unlike in most Caucasians, TPMT*3C is a common mutant allele in Kazaks, whereas TPMT*3A is a rare mutant allele. Further studies are needed to explore the clinical impact of these TPMT mutants to thiopurine therapy in Kazak patients.
Authors: D Otterness; C Szumlanski; L Lennard; B Klemetsdal; J Aarbakke; J O Park-Hah; H Iven; K Schmiegelow; E Branum; J O'Brien; R Weinshilboum Journal: Clin Pharmacol Ther Date: 1997-07 Impact factor: 6.875
Authors: Malin Lindqvist; Sofie Haglund; Sven Almer; Curt Peterson; Jan Taipalensu; Erik Hertervig; Ebbe Lyrenäs; Peter Söderkvist Journal: Pharmacogenetics Date: 2004-04
Authors: H L Tai; E Y Krynetski; C R Yates; T Loennechen; M Y Fessing; N F Krynetskaia; W E Evans Journal: Am J Hum Genet Date: 1996-04 Impact factor: 11.025
Authors: R Honchel; I A Aksoy; C Szumlanski; T C Wood; D M Otterness; E D Wieben; R M Weinshilboum Journal: Mol Pharmacol Date: 1993-06 Impact factor: 4.436