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Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

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Introduction to Genomics and Epigenomics Roles in Cardiovascular Diseases

Author and Curator: Larry H Bernstein, MD, FCAP

This introduction is to a thorough evaluation of a rich source of research literature on the genomic influences, which may have variable strength in the biological causation of atherosclerosis, microvascular disease, plaque formation, not necessarily having expressing, except in a multivariable context that includes the environment, dietary factors, level of emotional stress, sleep habits, and the daily activities of living for affected individuals. The potential of genomics is carried in the DNA, copied to RNA, and this is most well studied in the micro RNAs (miRNA). The miRNA has been explored for the appearance in the circulation of specific miRNAs that might be associated with myocyte or endothelial cell injury, and they are also being used as targets for therapeutics by the creation of silencing RNAs (siRNA). The extent to which there is evidence of success in these studies is limited, but is being translated from animal studies to human disease. There is also a long history of the measurement of circulating enzymes and isoenzymes (alanine amino transferase, creatine kinase, and lactate dehydrogenase, not to leave out the adenylate kinase species specific to myocardium), and more recently the release of troponins I and T, and the so far still not fully explored ischemia modified albumin, or of miRNAs for the diagnosis of myocardial infarction.

There is also a significant disagreement about the value of measuring high sensitivity C reactive protein (hs-CRP), which has always been a marker for systemic inflammatory disease, in both chronic rheumatic and infectious diseases having a broad range, so that procalcitonin has appeared to be better for that situation, and for early diagnosis of sepsis. The hs-CRP has been too easily ignored because of

1. the ubiquitous elevations in the population
2. the expressed concerns that one might not be inclined to treat a mild elevation without other risk factors, such as, LDL cholesterolemia, low HDL, absent diabetes or obesity. Nevertheless, hs-CRP raises an reasonable argument for preventive measures, and perhaps the use of a statin.

There has been a substantial amount of work on the relationship of obesity to both type 2 diabetes mellitus (T2DM) and to coronary vascular disease and stroke. Here we bring in the relationship of the vascular endothelium, adipose tissue secretion of adiponectin, and platelet activation. A whole generation of antiplatelet drugs addresses the mechanism of platelet activation, adhession, and interaction with endothelium. Very interesting work has appeared on RESISTIN, that could bear some fruit in the treatment of both obesity and T2DM.

It is important to keep in mind that epigenomic gene rearrangements or substitutions occur throughout life, and they may have an expression late in life. Some of the known epigenetic events occur with some frequency, but the associations are extremely difficult to pin down, as well as the strength of the association. In a population that is not diverse, epigenetic changes are passed on in the population in the period of childbearing age. The establishment of an epigenetic change is diluted in a diverse population. There have been a number of studies with different findings of association between cardiovascular disease and genetic mutations in the Han and also in the Uyger Chinese populations, which are distinctly different populations that is not part of this discussion.

This should be sufficient to elicit broad appeal in reading this volume on cardiovascular diseases, and perhaps the entire series. Below is a diagram of this volume in the series.

PART 1 – Genomics and Medicine
Introduction to Genomics and Medicine (Vol 3)
Genomics and Medicine: The Physician’s View
Ribozymes and RNA Machines
Genomics and Medicine: Genomics to CVD Diagnoses
Establishing a Patient-Centric View of Genomic Data

VIDEO: Implementing Biomarker Programs P Ridker	PART 2 – Epigenetics – Modifiable Factors Causing CVD
	Diseases Etiology
	Environmental Contributors Implicated as Causing CVD
	Diet: Solids and Fluid Intake and Nutraceuticals
	Physical Activity and Prevention of CVD
	Psychological Stress and Mental Health: Risk for CVD
	Correlation between Cancer and CVD

PART 3 Determinants of CVD – Genetics, Heredity and Genomics Discoveries

Introduction

Why cancer cells contain abnormal numbers of chromosomes (Aneuploidy)

Functional Characterization of CV Genomics: Disease Case Studies @ 2013 ASHG

Leading DIAGNOSES of CVD covered in Circulation: CV Genetics, 3/2010 – 3/2013

Commentary on Biomarkers for Genetics and Genomics of CVD

PART 4 Individualized Medicine Guided by Genetics and Genomics Discoveries

Preventive Medicine: Cardiovascular Diseases

Walking and Running: Similar Risk Reductions for Hypertension, Hypercholesterolemia,
DM, and possibly CAD
http://pharmaceuticalintelligence.com/2013/04/04/walking-and-running-similar-risk-reductions-for-hypertension-hypercholesterolemia-dm-and-possibly-cad/

Prevention of Type 2 Diabetes: Is Bariatric Surgery the Solution?
http://pharmaceuticalintelligence.com/2012/08/23/prevention-of-type-2-diabetes-is-bariatric-surgery-the-solution/

Gene-Therapy for CVD

Congenital Heart Disease/Defects

Medical Etiologies: EBM – LEADING DIAGNOSES, Risks		Pharmacogenomics for Cardio- vascular Diseases
Signaling Pathways		Response to Rosuvastatin in Patients With Acute Myocardial Infarction: Hepatic Metabolism and Transporter Gene Variants Effect http://pharmaceuticalintelligence.com/2014/ 01/02/response-to-rosuvastatin-in-patients- with-acute-myocardial-infarction-hepatic- metabolism-and-transporter-gene-variants-effect/
Proteomics and Metabolomics		Voltage-Gated Calcium Channel and Pharmaco- genetic Association with Adverse Cardiovascular Outcomes: Hypertension Treatment with Verapamil SR (CCB) vs Atenolol (BB) or Trandolapril (ACE) http://pharmaceuticalintelligence.com/2014/01/02/ voltage-gated-calcium-channel-and-pharmacogenetic- association-with-adverse-cardiovascular-outcomes- hypertension-treatment-with-verapamil-sr-ccb-vs- atenolol-bb-or-trandolapril-ace/
		SNPs in apoE are found to influence statin response significantly. Less frequent variants in PCSK9 and smaller effect sizes in SNPs in HMGCR http://pharmaceuticalintelligence.com/2014/01/02/snps-in-apoe-are-found-to-influence-statin-response-significantly-less-frequent-variants-in-pcsk9-and-smaller-effect-sizes-in-snps-in-hmgcr/