Human Pharmacogenomic Variation of Antihypertensive Drugs: From Population Genetics to Personalized Medicine

Abstract

Aim: To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes. Materials & methods: The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation. Results: Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs. Conclusion: Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs.

Original submitted 19 September 2013; Revision submitted 14 November 2013

KEYWORDS::

• bioinformatics
• blood pressure
• drugs
• geographic origin
• hypertension
• pharmacogenomics

Acknowledgements

The authors are grateful to the research groups of HGDP and of 1000 Genomes Project for their essential contributions.

Financial & competing interests disclosure

This study was supported by RSA Grant 2009 from University of Rome Tor Vergata, by PRIN 2009-2011 (prot. n. 200975T9EW) from MIUR, and by a grant from Fatebenefratelli Association for Biomedical Research (AFaR). 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 study was supported by RSA Grant 2009 from University of Rome Tor Vergata, by PRIN 2009-2011 (prot. n. 200975T9EW) from MIUR, and by a grant from Fatebenefratelli Association for Biomedical Research (AFaR). 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.