Genetic Biomarkers Associated with Cardiovascular Diseases
المؤلف:
Marcello Ciaccio
المصدر:
Clinical and Laboratory Medicine Textbook 2021
الجزء والصفحة:
p305
2025-09-09
255
The genomic analysis includes many procedures, very different from each other, which allow the identification of possible genes (candidate genes), whose altered function could be responsible for particular and rare forms of cardiovascular diseases (monogenic diseases). Additionally, some polymorphisms (gene variants) could be associated with an increased risk of cardiovascular events.
Malformations of the heart and great vessels account for a large proportion of congenital disabilities in about 1% of live births. Some of these forms may be caused by chromosomal alterations (such as deletion or translocation) or by mutations in a single gene. In addition, some of the idiopathic forms of dilated or hypertrophic myocardiopathy, especially familial forms, may be caused by the altered function of a single gene and be heritable. Finally, some familial forms of cardiac arrhythmias may also recognize a genetic basis because they are caused by an alteration in the function of a single or a few genes. In all these cases, the genetic test, if available, can not only confirm the diagnosis but also offer the opportunity for appropriate counseling in highly specialized departments and/or suggest new treatment protocols.
However, considering the cardiovascular system, the clinical utility of the analysis of possible candidate genes is theoretically limited by the fact that the most frequent dis orders affecting this system recognize a multifactorial etiology, in which both environmental and behavioral factors interact dynamically with the function of different genes in determining the pathophysiological mechanisms that will lead to the establishment of the cardiovascular disorder. For this reason, it is impossible to associate single genes’ to specific, persistent clinical conditions, such as acute coronary syndromes, hypertension, diabetes, and dyslipidemia, which recognize a complex multifactorial etiology. In these cases, a “genomic” or “proteomic” approach, rather than a genetic analysis based on a single gene locus or haplotype, has been more effectively suggested. The aim would be to define a profile or a fingerprint, recognized by molecular analysis or of the concomitant function of several genes or metabolites of the same biochemical pathway (gene clustering, expression patterns, proteomic fingerprint, or signature), associated with a specific cardiovascular disease. The limitations of this approach are that the analysis is expensive and available in few laboratories, and the results obtained are often not easily interpretable from a diagnostic and/or prognostic point of view, so this type of analysis is still not very usable in clinical practice.
Recently, the interest in studying the relationships between cardiovascular disease and gene expression has focused on the study of single-stranded RNAs, which may be present not only in the nucleus and cytoplasm of cells but also in the circulation. In particular, the focus has been on studying microRNAs (miRNAs), a class of small, noncoding RNAs that regulate the expression of complementary RNAs. Altered expression of intracellular miRNAs has been reported in many diseases, including cardiovascular diseases. In particular, many studies have recently high lighted the role of some miRNAs not only in some pathophysiological processes affecting the myocardium, such as fibrosis, hypertrophy, and angiogenesis, but also in some complex clinical conditions, such as dilated and hypertrophic myocardial diseases, myocardial infarction, and heart failure. Being circulating molecules, which can be assayed in blood samples by laboratory methods, miRNAs represent circulating biomarkers of disease and, therefore, do not present the limitations of the genomic or proteomic approach. A list of the most studied miRNAs as risk bio markers in patients with heart disease is shown in Table 1.
Table1. List of microRNAs (miRNAs) most studied as risk bio markers in patients with heart disease
Numerous meta-analyses have tried to evaluate the association of some of these circulating miRNAs with frequent cardiovascular disorders, such as stroke, ischemic heart dis ease, and heart failure. However, there are still some critical issues related to their use as biomarkers of cardiovascular diseases. First, it is not yet evident the relationship between the gene expression of these noncoding RNAs (e.g., in myocardiocytes) and their respective circulating levels. Moreover, the methods currently available for their measurement are not standardized, and there are no internationally agreed quality specifications, so results obtained in different laboratories and by different methods are not comparable. For these reasons, the identification and determination of these molecules are applicable only in the fields of pathophysiological and clinical research.
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