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Pharmacogenomics of Hypertension and Preeclampsia: Focus on Gene-Gene Interactions
Marcelo R Luizon1,2, Daniela A Pereira2, Valeria C Sandrim3
1Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
Insights
Pharmacogenomics, the study of how genes affect drug response, can personalize hypertension treatment. Gene interactions are crucial for understanding variable responses to antihypertensive drugs, especially in preeclampsia.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Genetics
Background:
- Hypertension and preeclampsia significantly contribute to cardiovascular mortality and morbidity.
- Many patients with hypertension and preeclampsia show poor response to antihypertensive therapies.
- Current treatments lack personalization, leading to suboptimal blood pressure control in a significant patient subset.
Purpose of the Study:
- To explore the role of pharmacogenomics in personalizing antihypertensive drug treatment.
- To highlight the importance of gene-gene interactions in understanding variable drug responses.
- To review recent findings and future directions in the pharmacogenetics of hypertension and preeclampsia.
Main Methods:
- Review of existing literature on pharmacogenomics and antihypertensive drug response.
- Analysis of gene-gene interactions within relevant biological pathways.
- Discussion of statistical methods for detecting complex genetic effects on drug response phenotypes.
Main Results:
- Evidence suggests genetic variants influence response to common antihypertensive drugs, but require population-specific replication.
- Gene-gene interaction analyses are increasingly applied in pharmacogenetic studies of antihypertensive response.
- Complex genetic effects involving multiple genes are critical for predicting drug response.
Conclusions:
- Pharmacogenomics offers a promising avenue for personalized antihypertensive therapy.
- Understanding gene-gene interactions is essential for unraveling complex genetic influences on drug response.
- Further research is needed to identify additional genes and variants impacting antihypertensive drug responsiveness.
Abstract:
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 non-responsive to antihypertensive therapy. Pharmacogenomics may help to guide the personalized treatment for non-responsive 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.
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