Unraveling New Therapeutic Targets of Coronary Artery Disease by Genetic Approaches

Abstract

Coronary artery disease (CAD) is the most common cause of death and physical disabilities in developed countries, even though efforts to identify and target causal factors such as hypertension and dyslipidemia have brought tremendous improvements in prevention and treatment. A rapid advance in technology has unraveled new genetic variants associated with CAD and also provided great opportunities to identify novel pathogenic mechanisms and to develop new drugs with higher specificity. Whole-genome sequencing and whole-exome sequencing has made it possible to find rare alleles that are responsible for CAD in small, affected families and case-control studies in a very efficient manner. At present, genome-wide association studies have identified more than 50 loci that explain approximately 10% of the heritability of CAD, most of which is unrelated to traditional risk factors. Mendelian randomization studies enable identification of causal factors among numerous biomarkers and to narrow down promising therapeutic targets. This review highlights new genetic approaches and demonstrates the extent to which the outcome contributes to the finding of new therapeutic targets. (Circ J 2015; 79: 8 -14)

Docosahexaenoic acid reversed atherosclerotic changes in human endothelial cells induced by palmitic acid in vitro

“…7 A plethora of evidence confirmed the potency of members of family long PTX (PTX-3) in promoting atherosclerosis. 10,11 Up to the present, reduction of low-density lipoprotein, application of anticoagulant drugs, percutaneous coronary intervention, and coronary artery bypass surgery have been considered as routine therapies for atherosclerosis. 9 An increased level of IL-6 during atherosclerotic exacerbates the pathological outcomes, and reduction of this interleukin has been shown to yield therapeutic effects.…”

“…9 An increased level of IL-6 during atherosclerotic exacerbates the pathological outcomes, and reduction of this interleukin has been shown to yield therapeutic effects. 10,11 Up to the present, reduction of low-density lipoprotein, application of anticoagulant drugs, percutaneous coronary intervention, and coronary artery bypass surgery have been considered as routine therapies for atherosclerosis. 12 In spite of these modulations, many attempts have been focused on the application of natural compound and alternative medicine.…”

Epidemiology: Then and Now

“…Better measures of exposure to the agents in the physical and social environments are critical to understanding the interrelationship among the specific genetic attributes, pathophysiology, and disease. Better evaluation of exposures to agents of disease and determinants of the phenotype, as well as newer, lower-cost genomic analyses, will more likely lead to advances in genetic epidemiology (113)(114)(115)(116)(117). Again, these studies will greatly benefit from new technologies and better and lower-cost data-collection methods for the investigation of epidemics.…”

Sex-specific association of SH2B3 and SMARCA4 polymorphisms with coronary artery disease susceptibility

“…Recent reports suggested that mutations in this gene cause small cell carcinoma of the ovary of hypercalcemic type [ 18 ], lung cancer [ 19 ], and other diseases [ 20 , 21 ]. Combining GWAS data and case-control studies, we reported the association of SMARCA4 with CAD risk [ 22 – 24 ]. To date, however, no studies investigated the possible correlations between SH2B3 and SMARCA4 genes and CAD susceptibility in the Chinese Han population.…”