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

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.