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Gene interactions in pharmacogenomics

Perspective ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.00168

Pharmacogenomics of Hypertension and Preeclampsia: Focus on Gene-gene Interactions

  • 1Department of General Biology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil
  • 2Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Programa de Posgrado en Genética, Universidade Federal de Minas Gerais, Brazil
  • 3Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Brazil

Hypertension is a leading cause of cardiovascular mortality, but only about half of patients on antihypertensive therapy achieve blood pressure control. Preeclampsia is defined as pregnancy-induced hypertension and proteinuria, and is associated with increased maternal and perinatal mortality and morbidity. Similarly, a large number of patients with preeclampsia are nonresponsive to antihypertensive therapy. Pharmacogenomics may help to guide the personalized treatment for nonresponsive hypertensive patients. There is evidence for the association of genetic variants with variable response to the most commonly used antihypertensive drugs. However, further replication is needed to confirm these associations in different populations. The failure to replicate findings from single-locus association studies has prompted the search for novel statistical methods for data analysis, which are required to detect the complex effects from multiple genes to drug response phenotypes. Notably, gene-gene interaction analyses have been applied to pharmacogenetic studies, including antihypertensive drug response. In this perspective article, we present advances of considering the interactions among genetic polymorphisms of different candidate genes within pathways relevant to antihypertensive drug response, and we highlight recent findings related to gene-gene interactions on pharmacogenetics of hypertension and preeclampsia. Finally, we discuss the future directions that are needed to unravel additional genes and variants involved in the responsiveness to antihypertensive drugs.

Keywords: Antihypertensive therapy, Gene-Gene Interactions, Epistasis, Hypertension, pathways, pharmacogenomics, Preeclampsia

Received: 01 Dec 2017; Accepted: 15 Feb 2018.

Edited by:

Wanqing Liu, Wayne State University, United States

Reviewed by:

Reginald F. Frye, College of Pharmacy, University of Florida, United States
Vijay Suppiah, University of South Australia, Australia  

Copyright: © 2018 Luizon, Pereira and Sandrim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marcelo R. Luizon, Universidade Federal de Minas Gerais, Department of General Biology, Institute of Biological Sciences, Avenida Presidente Antônio Carlos, 6627 - Pampulha, Belo Horizonte, 31270-901, Minas Gerais, Brazil,