This work was supported by the National Nature Science Fund of China (No. 30171098); Elite Grant from Higher Education Office of Guangdong Province, China (No.200032); Guangdong Nature Science Fund (No.200032)
Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy Chinese children: A comparison of Han and Yao ethnic groups
Article first published online: 4 JUN 2004
British Journal of Clinical Pharmacology
Volume 58, Issue 2, pages 163–168, August 2004
How to Cite
Zhang, J.-p., Guan, Y.-y., Wu, J.-h., Xu, A.-L., Zhou, S. and Huang, M. (2004), Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy Chinese children: A comparison of Han and Yao ethnic groups. British Journal of Clinical Pharmacology, 58: 163–168. doi: 10.1111/j.1365-2125.2004.02113.x
- Issue published online: 4 JUN 2004
- Article first published online: 4 JUN 2004
- Received 6 June 2003 Accepted 29 January 2004
- thiopurine S-methyltransferase;
Ethnicity is an important variable influencing drug response. Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs. Previous population studies have identified ethnic variations in both phenotype and genotype of TPMT, but limited information is available within Chinese population that comprises at least 56 ethnic groups. The current study was conducted to compare both phenotype and genotype of TPMT in healthy Han and Yao Chinese children.
TPMT activity was measured in healthy Chinese children by a HPLC assay (n = 213, 87 Han Chinese and 126 Yao Chinese). Allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) were used to determine the frequency of TPMT mutant alleles (TPMT*2, TPMT*3 A, TPMT*3B and TPMT*3C) in these children.
There was no significant difference in the mean TPMT activity between Han and Yao Chinese children. A unimodal distribution of TPMT activity in Chinese children was found and the mean TPMT activity was 13.32 ± 3.49 U ml−1 RBC. TPMT activity was not found to differ with gender, but tended to increase with age in Yao Chinese children. TPMT*2, TPMT*3B and TPMT*3A were not detected, and only one TPMT*3C heterozygote (Han child) was identified in 213 Chinese children. Erythrocyte TPMT activity of this TPMT*3C heterozygote was 12.36 U ml−1 RBC. The frequency of the known mutant TPMT alleles was 0.2%[1/426] in Chinese children.
The frequency distribution of RBC TPMT activity was unimodal. The frequency of the known mutant TPMT alleles in Chinese Children is low and TPMT*3C appears to be the most prevalent among the tested mutant TPMT alleles in this population.