Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Correlation between CYP2D6*10 Gene Mutation, and Structure and Function of its Encoding Protein

Ju-yi Li¹, Xiu-fang Wang², Zhao-qing Zhang², Yong-gang Chen¹, Ji-li Zou¹, Xiong Wang¹, Jin-hu Wu¹

¹Department of Pharmacy; ²Department of Rehabilitation, The Third Hospital of Wuhan, Wuhan, Hubei Province, 430060 China.

For correspondence:- Jin-hu Wu Email: lisan727@163.com

Received: 30 August 2013 Accepted: 16 January 2014 Published: 24 March 2014

Citation: Li J, Wang X, Zhang Z, Chen Y, Zou J, Wang X, et al. Correlation between CYP2D6*10 Gene Mutation, and Structure and Function of its Encoding Protein. Trop J Pharm Res 2014; 13(3):347-351 doi: 10.4314/tjpr.v13i3.5

© 2014 The authors.
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Abstract

Purpose: To investigate the gene polymorphism of CYP2D6*10 (C188T) in the Hui people and study its correlation between CYP2D6*10 gene mutation and structure and function of its encoding protein.

Methods: 150 unrelated Hui ethnic group volunteers participated in this study. A total of 500 µL heparin-treated blood from each volunteer was extracted with the TIANGEN DNA Mini Kit. Allele specific amplification PCR and Gene sequencing were used to detect the CYP2D6 alleles *10. Bioinformatics and computer modeling methods were used to predict the spatial structure and function of the protein encoded by the wild type gene and mutant gene.

Results: The mutation frequency of C188T allele (T) of CYP2D6*10 in Ningxia Hui people was 47.5 %, compared with Turkish (14.5 %), Ethiopia (8.6 %), Spanish (1.9 %), and they were significantly different, (p < 0.01;) The result from ProtParam shows that mutant protein was more unstable than the wild-type protein. The isoelectric point, molecular weight and hydrophilicity were similar in terms of mutant protein and wild-type protein. Analysis of the gene sequence of CYP2D6*10 using DNAStar/Protein software indicates that the mutant protein had one more Gamier-Robson Turn while MotifScan analysis showed that the wild-type protein had 2 P450 enzyme activation sites and that there was none in the mutant protein. Analysis using SignalP demonstrated that the wild-type protein had signal peptide while the mutant protein had none. Analysis using TMHMM Server showed that both of them had a transmembrane region. The foregoing differences between the mutant protein and the wild-type protein could influence the activity of CYP2D6.

Conclusion: Gene mutation can change the spatial structure and function of CYP2D6. This change may be the main reason for the decreased activity of the enzyme.

Keywords: Polymorphism, CYP2D6, Mutant, Allele, Protein, Gene, Bioinformatics, Personalized medicine