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Published on: April 1, 2019
Polymorphisms in common antihypertensive targets: Pharmacogenomic implications for the treatment of cardiovascular
Dominique Brown1, Heather Alcala1, Peter Oelschlaeger1
1Western University of Health Sciences, Pomona, CA, United States.
Insights
Personalized medicine can improve hypertension treatment by analyzing genetic variations in drug targets. Understanding these polymorphisms helps tailor antihypertensive medications for better patient outcomes.
Area of Science:
- Genomics
- Pharmacology
- Cardiovascular Medicine
Background:
- Personalized medicine, driven by genome sequencing, has yet to fully impact clinical practice.
- Cardiovascular diseases are a leading global cause of death, with hypertension as a major precursor.
- Hypertension is an ideal model for personalized medicine due to its prevalence and available drug targets.
Purpose of the Study:
- To survey genetic polymorphisms in key antihypertensive drug targets.
- To investigate the impact of these polymorphisms on drug treatment variability.
- To highlight the potential of pharmacogenomics in optimizing hypertension management.
Main Methods:
- Visual depiction of polymorphisms in the eight primary antihypertensive targets.
- Review of existing genome-wide association studies and their focus on drug treatment.
- Leveraging recent technological advancements for polymorphism analysis (e.g., high-throughput screening, CRISPR).
Main Results:
- Over 17,000 polymorphisms identified across the examined drug target proteins.
- Strong expectation that polymorphisms contribute significantly to clinical variability in hypertension treatment.
- Demonstration of how advanced techniques enable rapid assessment of polymorphism effects on drug interactions.
Conclusions:
- Hypertension is a suitable disease for pharmacogenomic studies due to ease of measurement and numerous drug options.
- A comprehensive examination of how genetic polymorphisms affect drug efficacy is crucial for realizing personalized medicine.
- Genotype-guided prescribing can lead to optimized, individualized hypertension therapy.
Abstract:
The idea of personalized medicine came to fruition with sequencing the human genome; however, aside from a few cases, the genetic revolution has yet to materialize. Cardiovascular diseases are the leading cause of death globally, and hypertension is a common prelude to nearly all cardiovascular diseases. Thus, hypertension is an ideal candidate disease to apply tenants of personalized medicine to lessen cardiovascular disease. Herein is a survey that visually depicts the polymorphisms in the top eight antihypertensive targets. Although there are numerous genome-wide association studies regarding cardiovascular disease, few studies look at the effects of receptor polymorphisms on drug treatment. With 17,000+ polymorphisms in the combined target proteins examined, it is expected that some of the clinical variability in the treatment of hypertension is due to polymorphisms in the drug targets. Recent advances in techniques and technology, such as high throughput examination of single mutations, structure prediction, computational power for modeling, and CRISPR models of point mutations, allow for a relatively rapid and comprehensive examination of the effects of known and future polymorphisms on drug affinity and effects. As hypertension is easy to measure and has a plethora of clinically viable ligands, hypertension makes an excellent disease to study pharmacogenomics in the lab and the clinic. If the promises of personalized medicine are to materialize, a concerted effort to examine the effects polymorphisms have on drugs is required. A clinician with the knowledge of a patient's genotype can then prescribe drugs that are optimal for treating that specific patient.
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