Han Chinese specific cytochrome P450 polymorphisms and their impact on the metabolism of anti-hypertensive drugs with adrenoreceptor blocking properties

ABSTRACT

Introduction: Cytochrome P450 (CYP) is a monooxygenase superfamily mediating the elimination of anti-hypertensive drugs. Polymorphisms of CYP would lead to differential drug efficacy. Building relationships between genotype and phenotype will benefit individual medical treatment of hypertension.

Areas covered: The review systematically summarizes the polymorphisms of four CYPs (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) concentrated distributed in the Han Chinese population. Moreover, the activity of variants on metabolizing anti-hypertensive drugs are reviewed, especially drugs with adrenoceptor blocking properties, as well as their clinical relevancies.

Expert opinion: The polymorphisms of CYP can cause stratification in drug exposure of antihypertensive drugs. Although the clinical relevance has been built partially, the translational medicine still lacks reliable data support. Furthermore, the studies have demonstrated that even the same CYP variant will exhibit different catalytic capability for different drugs, which is another obstacle to hinder its application. With the deepening of multiomics research and structural biology, nucleotide polymorphisms can be combined with transcriptome, proteome, metabolome and molecular structure analyses to study the susceptibility to hypertension and drug efficacy. A complete data chain would be further estabolished by combining studies of pharmacokinetics-pharmacodynamics, which can effectively promote the precise application of anti-hypertensive drugs.

KEYWORDS:

• Cytochrome P450
• polymorphism
• intrinsic clearance
• anti-hypertensive drugs
• han chinese

Article highlights

• There are many genetic polymorphisms concentrated distribution in the Han Chinese population, concerning CYP2C9, CYP2C19, CYP2D6 and CYP3A4.

• The frequency of novel haploid allelic variants is about 1/5000, suggesting that the world population still contains abundant CYP polymorphic loci.

• CYPs are involved in the primary metabolic pathway in the elimination of anti-hypertensive drugs, especially adrenoceptor blocking drugs.

• The enzymatic activities of mentioned CYP variants are reduced significantly, leading to decrease the clearance rate of anti-hypertensive drugs with adrenoceptor blocking properties.

• There are still obstacles to translational medicine based on CYP genotype, and multidisciplinary research need to be carried out to promote the application.

Acknowledgments

The authros thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Declaration of interest

The authors have no relevant affiliation 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, and royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded from the National Natural Science Foundation of China (81973397).