Abstract
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- and anti-inflammatory cytokines, Toll-like receptor 4 (TLR4), CD14, CCR5, cyclooxygenases (COXs) and lipoxygenases (LOXs). The associations between candidate gene polymorphisms and CHD/MI are difficult and complex as a consequence of pleiotropy, variations with age, selection due to the lethality of the disease, and interactions with other genes and environmental factors. However, current data indicate that screening for interleukin (IL)-6, IL-10, TLR4, CCR5, COX and LOX polymorphisms are likely to be a useful tool for CHD and MI risk assessment. What we believe is that dissecting out the influence of genetics polymorphism within the complex pathophysiology of CHD and MI will help to provide a more complete risk assessment and complement known classical cardiological risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug of lifestyle modification.
Keywords: CD14, CCR5, COX, cytokines, LOX, myocardial infarction, pharmacogenomics, TLR4
Current Pharmaceutical Design
Title: Pharmacogenomics: A Tool to Prevent and Cure Coronary Heart Disease
Volume: 13 Issue: 36
Author(s): Giuseppina Candore, Carmela Rita Balistreri, Marco Caruso, Maria Paola Grimaldi, Egle Incalcaterra, Florinda Listi, Sonya Vasto and Calogero Caruso
Affiliation:
Keywords: CD14, CCR5, COX, cytokines, LOX, myocardial infarction, pharmacogenomics, TLR4
Abstract: Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- and anti-inflammatory cytokines, Toll-like receptor 4 (TLR4), CD14, CCR5, cyclooxygenases (COXs) and lipoxygenases (LOXs). The associations between candidate gene polymorphisms and CHD/MI are difficult and complex as a consequence of pleiotropy, variations with age, selection due to the lethality of the disease, and interactions with other genes and environmental factors. However, current data indicate that screening for interleukin (IL)-6, IL-10, TLR4, CCR5, COX and LOX polymorphisms are likely to be a useful tool for CHD and MI risk assessment. What we believe is that dissecting out the influence of genetics polymorphism within the complex pathophysiology of CHD and MI will help to provide a more complete risk assessment and complement known classical cardiological risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug of lifestyle modification.
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Candore Giuseppina, Balistreri Rita Carmela, Caruso Marco, Grimaldi Paola Maria, Incalcaterra Egle, Listi Florinda, Vasto Sonya and Caruso Calogero, Pharmacogenomics: A Tool to Prevent and Cure Coronary Heart Disease, Current Pharmaceutical Design 2007; 13 (36) . https://dx.doi.org/10.2174/138161207783018617
DOI https://dx.doi.org/10.2174/138161207783018617 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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