Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 13, No. 3, 2014, pp. 347-351
Bioline Code: pr14050
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 13, No. 3, 2014, pp. 347-351
© Copyright 2014 - Tropical Journal of Pharmaceutical Research
Correlation between CYP2D6*10 Gene Mutation, and Structure and Function of its Encoding Protein|
Li, Ju-yi; Wang, Xiu-fang; Zhang, Zhao-qing; Chen, Yong-gang; Zou, Ji-li; Wang, Xiong & Wu, Jin-hu
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.
Polymorphism; CYP2D6; Mutant; Allele; Protein; Gene; Bioinformatics; Personalized medicine
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