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Phenotyping and genotyping study of thiopurine S‐methyltransferase in healthy Chinese children: A comparison of Han and Yao ethnic groups
Author(s) -
Zhang Jianping,
Guan Yongyuan,
Wu Jueheng,
Xu AnLong,
Zhou Shufeng,
Huang Min
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02113.x
Subject(s) - thiopurine methyltransferase , genotyping , genotype , allele frequency , heterozygote advantage , allele , chinese population , genetics , medicine , biology , gene , azathioprine , disease
Aims 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. Methods 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. Results 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. Conclusion 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.