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Genetic analysis of drug metabolizing phase-I enzymes CYP3A4 in Tibetan populations

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Abstract

The enzymatic activity of CYP3A4 results in broad interindividual variability in response to certain pharmacotherapies. The present study aimed to screen Tibetan volunteers for CYP3A4 genetic polymorphisms. Previous research has focussed on Han Chinese patients, while little is known about the genetic variation of CYP3A4 in the Tibetan populations. Here, we adopted DNA sequencing to investigate the promoter, exons and surrounding introns, and 3 ′-untranslated region of the CYP3A4 gene in 96 unrelated healthy Tibetan individuals. We identified 20 different CYP3A4 polymorphisms in the Tibetan population, including two novel variants (21824 A > G and 15580 G > C). In addition, we also determined the allele frequencies of CYP3A4*1A and CYP3A4*1H were 82.29% and 28.13%, respectively. CYP3A4*1P and *1G were relatively rare with frequencies of only 1.04% and 0.52%, respectively. Our results provide information on CYP3A4 polymorphisms in Tibetan individuals which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.

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Acknowledgements

This work was supported by National Natural Science Foundation (no. 81560516), Major science and technology research projects of Xizang (Tibet) Autonomous Region (2015XZ01G23), Natural Science Foundation of Tibet Autonomous Region (2015ZR-13-19), and The Project of Young Teachers’ Innovative Support Programme in Universities of Xizang (Tibet) Autonomous Region (no. QCZ2016-29).

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Author notes

  1. Lijun Liu and Yu Chang contributed equally to this work

Authors and Affiliations

  1. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China

    LIJUN LIU, LONGLI KANG, TIANBO JIN, DONGYA YUAN & YONGJUN HE

  2. Key Laboratory for Basic life science Research of Tibet autonomous region, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China

    LIJUN LIU, LONGLI KANG, TIANBO JIN, DONGYA YUAN & YONGJUN HE

  3. Key Laboratory of High Altitude Environment and Gene Related to Disease of Tibet Ministry of Education, Xizang Minzu University, Xianyang, 712082, Shaanxi, People’s Republic of China

    LIJUN LIU, LONGLI KANG, TIANBO JIN, DONGYA YUAN & YONGJUN HE

  4. Department of pharmacy, Hong-Hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, 710054, Shaanxi, People’s Republic of China

    YU CHANG

  5. Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi, 710075, People’s Republic of China

    SHULI DU, XUGANG SHI, HUA YANG & TIANBO JIN

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  1. LIJUN LIU
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  2. YU CHANG
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  3. SHULI DU
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  4. XUGANG SHI
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  5. HUA YANG
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  6. LONGLI KANG
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  7. TIANBO JIN
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  8. DONGYA YUAN
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  9. YONGJUN HE
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Corresponding authors

Correspondence to DONGYA YUAN or YONGJUN HE.

Additional information

Corresponding editor: Shantanu Sengupta

[Liu L., Chang Y., Du S., Shi X., Yang H., Kang L., Jin T., Yuan D. and He Y. 2017 Genetic analysis of drug metabolizing phase-I enzymes CYP3A4 in Tibetan populations. J. Genet. 96, xx–xx]

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LIU, L., CHANG, Y., DU, S. et al. Genetic analysis of drug metabolizing phase-I enzymes CYP3A4 in Tibetan populations. J Genet 96, 219–225 (2017). https://doi.org/10.1007/s12041-017-0757-z

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  • DOI: https://doi.org/10.1007/s12041-017-0757-z

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