Cardiovascular pharmacogenetics: a promise for genomically‐guided therapy and personalized medicine

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter-individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic-based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed.

Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy

“…As such, future evidence-based research to improve the care of patients of cancer survivors should focus on the following areas: (1) improvement in our understanding of the precise molecular and pathophysiological mechanisms of cardiotoxicity; (2) improvement in risk prediction that allows targeted treatment and avoidance of unnecessarily burdensome therapies for patients most likely to develop cardiotoxicity; (3) randomized controlled trials comparing surveillance frequency for cardiotoxicity prevention and superiority of different treatment strategies on minimizing and preventing cardiovascular complications. The widely advocated precision medicine encompassing “big data” and omics including pharmacogenetics-pharmacogenomics 127 , 128 would fit perfectly well to the urgently needed area of cardio-oncology research and clinical care. Finally, the multidisciplinary approach of cardio-oncology service with close collaborations among oncologists, cardiologists, and other allied health care professionals will be essential in the development and promotion of clinical care models to improve long-term outcomes of cancer treatments and cancer survivors.…”

Examining How Our Shared Evolutionary History Shapes Future Disease Outcomes

“…Furthermore, genomic advances have started transforming medical care by facilitating inclusion of genetic variants for diagnosis and treatment. As an illustrative example, the field of pharmacogenomics is built on the promise of delivering precision care based on our understanding of genetic variants and their associated risks [30-32]. To deliver this promise to all individuals, the chasm in ancestral diversity of study participants that have remained less represented in GWAS should be addressed [8].…”

The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder

“…Pharmacogenetics is a research field encompassing the analysis of gene variants that are associated with the variability of drug response and adverse drug reaction. This field has grown rapidly and some of the results have been implemented in clinical practice for personalized drug treatment [ 16 - 18 ]. MPH treatment is considered effective and safe for ADHD patients, with a response rate of 65–80% [ 2 , 19 , 20 ], but there was considerable inter-individual variability among patients regarding response to treatment, required doses, and adverse events [ 11 ].…”