Cardiovascular Precision Medicine in the Genomics Era

Abstract

SummaryPrecision medicine strives to delineate disease using multiple data sources—from genomics to digital health metrics—in order to be more precise and accurate in our diagnoses, definitions, and treatments of disease subtypes. By defining disease at a deeper level, we can treat patients based on an understanding of the molecular underpinnings of their presentations, rather than grouping patients into broad categories with one-size-fits-all treatments. In this review, the authors examine how precision medicine, specifically that surrounding genetic testing and genetic therapeutics, has begun to make strides in both common and rare cardiovascular diseases in the clinic and the laboratory, and how these advances are beginning to enable us to more effectively define risk, diagnose disease, and deliver therapeutics for each individual patient.

The Role of CYP450 Drug Metabolism in Precision Cardio-Oncology

“…Interindividual variability is largely heritable [1,2,7,69,111], thus stimulating interest in utilizing personalization tools such as pharmacogenomics (i.e., the impact of genome variations on individual response to therapeutics) in patient care [2,7,[112][113][114][115][116].…”

“…To illustrate, a notable example in precision cardiovascular medicine is CYP2C9 genotype-guided dosing of the commonly used anticoagulant warfarin [112,117]. The Clinical Pharmacogenetic Implementation Consortium (CPIC) is an initiative focused on integrating pharmacogenomics into routine clinical care.…”

“…This may be, at least in part, due to the seemingly inconsistent results of various studies examining the potential impact of genetic testing to guide warfarin dosing. For example, the EU-PACT, GIFT and COAG studies are studies all investigating the utility, efficacy, cost and benefit of genetic testing to guide warfarin dosing decisions [112,117,118,120,121]. The two former studies were conducted largely in homogenous populations (>90% European ancestry), whereas the COAG study was conducted in a more diverse population in the US (28% of trial participants were African American) and did not show a great benefit to warfarin pharmacogenomics [117,120].…”

“…However, while EU-PACT administered a loading dose (according to American College of Chest Physicians guidelines) upon initiation of warfarin, the COAG study did not [121][122][123]. Warfarin-related variants have been less studied among African and Hispanic populations, which is notable as there is higher dose variability in these ethnic populations [112,117]. To date, no study has accounted for CYP2C9 variants more common in African Americans (*5, *6, *8, *11).…”

Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis

“…Single nucleotide polymorphisms (SNPs) are DNA sequence polymorphisms caused by a single nucleotide variation at the genome level and are the most common human genetic variants [3]. Genome-wide association studies (GWASs) have enabled the discovery of common genetic variation contributing to normal and pathological traits [4,5], suggesting that the use of SNPs as biomarkers is useful for the screening of susceptible populations and is conducive to genetic diagnosis, gene therapy for hypertension [6,7].…”