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Phenotyping and Genotyping Studies of Thiopurine S-Methyltransferase in Kazaks

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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.

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Abbreviations

6-MP:

6-mercaptopurine

PCR:

polymerase chain reaction

TPMT:

thiopurine S-methyltransferase

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Acknowledgments

The authors thank Dr. Weinshilboum (Mayo Medical School, Mayo Clinic, Rochester, NY, USA) for providing DNA reference samples. This work was supported by the National Nature Science Fund of China (No.30171098), Guangdong Nature Science Fund (No. 36622), China Ministry of Education Fund for Phd Training Site (No. 20030558081), and National University of Singapore Academic Research Fund (No. R-148-000-047-101).

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Shenzhen Children's Hospital, Shenzhen, People's Republic of China

    Hong Wei & Chengrong Li

  2. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore

    Shufeng Zhou

  3. Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat Sen University, 74 Zhongshan Er Road, Guangzhou, 510080, People's Republic of China

    Jianping Zhang, Jueheng Wu & Min Huang

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  1. Hong Wei
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  2. Shufeng Zhou
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  3. Chengrong Li
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Correspondence to Min Huang.

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Wei, H., Zhou, S., Li, C. et al. Phenotyping and Genotyping Studies of Thiopurine S-Methyltransferase in Kazaks. Pharm Res 22, 1762–1766 (2005). https://doi.org/10.1007/s11095-005-7095-1

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