Pharmacogenomics: A Tool to Prevent and Cure Coronary Heart Disease

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.

Genotyping of Sex Hormone-Related Pathways in Benign and Malignant Human Prostate Tissues: Data of a Preliminary Study

“…Our data also imply that alleles associated with age-related diseases, including PCa, are not prominent in the genetic profile favouring longevity, as indicated in our previous studies (Candore et al, 2007a(Candore et al, , 2007b. Based on this evidence, one could speculate that the genes selected in our study may function in an antagonistically pleiotropic manner.…”

Is the Mean Blood Leukocyte Telomere Length a Predictor for Sporadic Thoracic Aortic Aneurysm? Data from a Preliminary Study

“…6 On the other hand, we have particularly outlined in our studies the key role of inflammation in CVD pathophysiology. 15,16 Accordingly, it is plausible that the actual length of the telomere in the vessel wall has less to do with the process of aging and is simply the result of an inflammatory process that shortens telomeres in parallel in many tissues. 6 In the light of these observations, we examined whether the mean of blood leukocyte telomere length might be a predictor for S-TAA.…”

Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

“…Accordingly, several studies have analyzed the association between inflammatory gene polymorphisms and atherosclerosis and myocardial infarction (MI) [93][94][95]. In a case-control study on MI, SNPs in several inflammatory genes, such as IL-1 , IL-6, IL-10, -1-antichymotrypsin, TNF-and interferon(IFN)-genes along with SNPs of genes regulating vascular functions (vascular endothelial growth factor; VEGF) and cholesterol synthesis (hydroxymethylglutaryl CoA reductase; HMGCR) were investigated.…”

“…Some of the studies here outlined allow building a risk profile that potentially enables the early identification of individuals susceptible to disease and the possible design or use of drug at the right dose for a desired effect, that is, a pharmacogenomic approach for a given disease [40,94].…”