Ju-yi Li1,
Xiu-fang Wang2,
Zhao-qing Zhang2,
Yong-gang Chen1,
Ji-li Zou1,
Xiong Wang1,
Jin-hu Wu1 
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.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
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.
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