Novel DNA Sequence Variations of Cytochrome P450 Genes in the Han Chinese Population

Abstract

Aim: Cytochrome P450 is an important monooxygenase responsible for the metabolism of a large variety of structurally diverse compounds. The aim of this study was to systematically investigate the DNA sequence variations in 14 cytochrome P450 genes relevant to drug metabolism in the Han Chinese population. Materials & methods: We sequenced these 14 genes in 23 subjects and determined the allele frequencies. Results: We identified a total of 312 genetic variants, which included 80 (25.6%) novel variants. These novel variants included 67 noncoding variants, four synonymous and nine nonsynonymous variants. Among these variants, an 11-nucleotide insertion in the 3´-flanking site of intron 6 in CYP2E1 (c.968-77_-76insGATGGGTGGAT) had the highest allele frequency of 0.565. A total of 16 of these novel variants were predicted to have potential functional consequences; however, among them only c.-1299T>A in CYP2C18 and c.-498C>A in CYP2D6 reached a frequency of 4.9%. Conclusions: This study establishes a genetic database of cytochrome P450 genes in the Han Chinese population and suggests further genetic diversity throughout this important gene family.

KEYWORDS::

• cytochrome P450
• direct sequence
• Han Chinese
• novel variants
• Taiwan

Financial & competing interests disclosure

This work was supported by grants from the National Research Program for Genomic Medicine, Taiwan (National Clinical Core, NSC -95-3112-B-001-010 and National Genotyping Core, NSC-95-3112-B-001-011), and the Genomics and Proteomics Program, Academia Sinica. None of the authors had any financial interest, directly or indirectly, that might affect the reporting of the work which has been submitted. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by grants from the National Research Program for Genomic Medicine, Taiwan (National Clinical Core, NSC -95-3112-B-001-010 and National Genotyping Core, NSC-95-3112-B-001-011), and the Genomics and Proteomics Program, Academia Sinica. None of the authors had any financial interest, directly or indirectly, that might affect the reporting of the work which has been submitted. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.