1. Phenotyping and Genotyping Studies of Thiopurine S-Methyltransferase in Kazaks
- Author
-
Jian-ping Zhang, Shu-Feng Zhou, Hong Wei, Min Huang, Chengrong Li, and Jue-heng Wu
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Mutant allele ,Pharmaceutical Science ,Biology ,Gene mutation ,law.invention ,Thiopurine S-Methyltransferase ,law ,Humans ,Pharmacology (medical) ,Allele frequency ,Genotyping ,Alleles ,Polymerase chain reaction ,Pharmacology ,Genetics ,Thiopurine methyltransferase ,Organic Chemistry ,Methyltransferases ,Middle Aged ,Molecular biology ,Unimodal distribution ,Kazakhstan ,Phenotype ,Mutation ,biology.protein ,Molecular Medicine ,Female ,Biotechnology - Abstract
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. 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. 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. 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.
- Published
- 2005
- Full Text
- View/download PDF