Editorial comment
Genetics and myocardial infarction
Genética e enfarte do miocárdio
Joana Barbosa Melo
Laboratório de Citogenética e Genómica, CNC.IBILI, CIMAGO, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal
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"apellidos" => "Monteiro" ] 9 => array:2 [ "nombre" => "António" "apellidos" => "Almeida-Dias" ] 10 => array:2 [ "nombre" => "Begoña" "apellidos" => "Criado" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204918303143?idApp=UINPBA00004E" "url" => "/21742049/0000003700000009/v2_201911291446/S2174204918303143/v2_201911291446/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Genetics and myocardial infarction" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "737" "paginaFinal" => "738" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Joana Barbosa Melo" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Joana Barbosa" "apellidos" => "Melo" "email" => array:1 [ 0 => "mmelo@fmed.uc.pt" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Laboratório de Citogenética e Genómica, CNC.IBILI, CIMAGO, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Genética e enfarte do miocárdio" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Genetic information is being increasingly used as part of individual clinical care, and genomic medicine is having an impact in several medical fields, especially in rare and undiagnosed diseases but also in oncology, pharmacology, and cardiology, among others. The ability to use genomic information to improve health is a direct result of the Human Genome Project (HGP), but translation of new discoveries into use in patient care can take years. Since completion of the HGP the focus has been on understanding how variations in an individual's DNA may affect disease and health, clarifying disease etiologies and prognosis, identifying variants that confer disease susceptibility, and improving the efficacy and safety of pharmacological treatments.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Discoveries in cardiovascular genetics are increasingly moving from bench to bedside and becoming more and more relevant to the clinical management of patients.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This field encompasses a wide variety of inherited cardiac conditions, including monogenic diseases such as various channelopathies and cardiomyopathies, and, although still at a very early stage, some disorders with a more complex inheritance pattern.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Myocardial infarction (MI) is a complex multifactorial disorder caused by the interaction of environmental and genetic factors. It is the most severe type of coronary artery disease (CAD) and one of the leading causes of death worldwide. Several risk factors for MI have been identified, particularly hypertension, dyslipidemia, diabetes and smoking.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Various studies have also addressed the importance of genetic factors, but despite the progress in cardiovascular genetics, data on the genetic background of MI are still limited and somewhat inconsistent.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Clinical and population-based studies have long shown that a positive family history for MI is a major cardiovascular risk factor. However, the heterogeneity of CAD and its clinical complications introduce significant complexity in genetic studies,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> and the range of genes underlying the heritable component of MI is not fully known. The Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease (CARDIoGRAMplusC4D) consortium is an example of a collaborative effort to combine data from multiple large-scale genetic studies to identify risk loci for CAD and MI.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Current knowledge of genetic variants affecting risk of CAD is largely based on analysis of common single-nucleotide polymorphisms (SNPs) in genome-wide association studies.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Several genetic loci have been associated with CAD and it appears that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> In the context of CAD and MI, as for other disorders with complex inheritance patterns, it is also important to consider epigenetic mechanisms that regulate the expression of these genes, and interactions between multiple genes and between these genes and environmental factors, as well as isolated genetic risk factors.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Knowledge of the genetic factors associated with the risk of MI is of particular importance for clinical management. Coronary atherosclerosis underlies the occurrence of MI in the majority of cases, and factors such as plaque vulnerability and the extent of thrombotic reaction to plaque disruption may predispose to MI in the presence of CAD.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> It is accepted that the rupture of a vulnerable atherosclerotic plaque, local activation of thrombotic mechanisms with or without severe underlying stenosis, local thrombosis formation and arterial lumen closure are the mechanisms most often underlying acute MI.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In the current issue of the <span class="elsevierStyleItalic">Journal</span>, Pina-Cabral et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> analyze the potential role of eight polymorphisms in four genes coding for platelet receptors, <span class="elsevierStyleItalic">GP1BA</span>, <span class="elsevierStyleItalic">ITGB3</span>, <span class="elsevierStyleItalic">ITGA2</span> and <span class="elsevierStyleItalic">P2RY12</span>, as risk factors for MI. It is known that platelet G protein-coupled receptors are critical regulators of platelet function, and it has been hypothesized that increased platelet activity at the site of atherosclerotic plaque rupture may result in MI.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Pina-Cabral et al.’s study has several limitations that are clearly stated by the authors, including the low numbers of patients and polymorphisms studied and heterogeneity between the control and MI groups, which limit the conclusions of the study. Despite its limitations, the paper assesses these polymorphisms in a Portuguese population and underlines the importance of fully understanding the genetic factors and molecular mechanisms behind the pathogenesis of MI, highlighting the need for further studies addressing genetic risk factors for MI.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Previously, genetic testing was based on conventional techniques like Sanger sequencing, analyzing genes one by one, but recent advances in DNA sequencing technologies have made it possible to investigate large numbers of disease genes simultaneously.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> These new sequencing methods, known as next-generation sequencing (NGS), are able to maximize the number of bases sequenced in the least amount of time, generating a wealth of data that can be used to understand complex phenotypes. These techniques are providing researchers and clinicians with a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Not surprisingly, clinical screening tools for whole-exome or genome sequencing are now entering the clinical domain, and the results they generate are beginning to be used by different medical specialties, including cardiology. With this in mind, as a final remark, it is important to emphasize that as genetic testing advances and NGS technologies become more accessible and affordable, training in cardiovascular genetics will be critical to ensure that the cardiological community is able to provide effective high-quality care for patients and families.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Implementing genome-driven personalized cardiology in clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 8 | 25 |
| 2024 October | 226 | 34 | 260 |
| 2024 September | 195 | 37 | 232 |
| 2024 August | 187 | 26 | 213 |
| 2024 July | 185 | 27 | 212 |
| 2024 June | 155 | 28 | 183 |
| 2024 May | 127 | 25 | 152 |
| 2024 April | 187 | 28 | 215 |
| 2024 March | 165 | 29 | 194 |
| 2024 February | 117 | 26 | 143 |
| 2024 January | 236 | 32 | 268 |
| 2023 December | 188 | 34 | 222 |
| 2023 November | 212 | 32 | 244 |
| 2023 October | 211 | 17 | 228 |
| 2023 September | 139 | 24 | 163 |
| 2023 August | 155 | 13 | 168 |
| 2023 July | 159 | 9 | 168 |
| 2023 June | 154 | 31 | 185 |
| 2023 May | 167 | 37 | 204 |
| 2023 April | 169 | 10 | 179 |
| 2023 March | 182 | 27 | 209 |
| 2023 February | 146 | 17 | 163 |
| 2023 January | 129 | 18 | 147 |
| 2022 December | 99 | 29 | 128 |
| 2022 November | 161 | 34 | 195 |
| 2022 October | 112 | 32 | 144 |
| 2022 September | 107 | 33 | 140 |
| 2022 August | 72 | 41 | 113 |
| 2022 July | 74 | 41 | 115 |
| 2022 June | 58 | 53 | 111 |
| 2022 May | 86 | 42 | 128 |
| 2022 April | 71 | 25 | 96 |
| 2022 March | 63 | 36 | 99 |
| 2022 February | 74 | 57 | 131 |
| 2022 January | 99 | 35 | 134 |
| 2021 December | 57 | 28 | 85 |
| 2021 November | 55 | 33 | 88 |
| 2021 October | 76 | 50 | 126 |
| 2021 September | 72 | 33 | 105 |
| 2021 August | 63 | 32 | 95 |
| 2021 July | 59 | 15 | 74 |
| 2021 June | 83 | 43 | 126 |
| 2021 May | 104 | 53 | 157 |
| 2021 April | 212 | 75 | 287 |
| 2021 March | 130 | 37 | 167 |
| 2021 February | 78 | 24 | 102 |
| 2021 January | 55 | 28 | 83 |
| 2020 December | 48 | 20 | 68 |
| 2020 November | 70 | 12 | 82 |
| 2020 October | 62 | 20 | 82 |
| 2020 September | 107 | 21 | 128 |
| 2020 August | 47 | 8 | 55 |
| 2020 July | 46 | 11 | 57 |
| 2020 June | 77 | 11 | 88 |
| 2020 May | 53 | 12 | 65 |
| 2020 April | 47 | 9 | 56 |
| 2020 March | 33 | 5 | 38 |
| 2020 February | 134 | 49 | 183 |
| 2020 January | 24 | 10 | 34 |
| 2019 December | 39 | 10 | 49 |
| 2019 November | 81 | 14 | 95 |
| 2019 October | 23 | 9 | 32 |
| 2019 September | 13 | 8 | 21 |
| 2019 August | 13 | 12 | 25 |
| 2019 July | 14 | 10 | 24 |
| 2019 June | 24 | 22 | 46 |
| 2019 May | 20 | 15 | 35 |
| 2019 April | 21 | 21 | 42 |
| 2019 March | 9 | 11 | 20 |
| 2019 February | 9 | 10 | 19 |
| 2019 January | 9 | 7 | 16 |
| 2018 December | 10 | 13 | 23 |
| 2018 November | 15 | 16 | 31 |
| 2018 October | 63 | 27 | 90 |
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