Authors details

1. Khyber Medical University, Peshawar Pakistan.

The incidence of Coronary artery disease (CAD) decreased significantly following implementation of primary and secondary prevention strategies like promotion of healthy life style, cessation of smoking, positive changes in nutrition and more emphasis on physical activity besides effective medical treatment like platelet inhibitors and Statins in the later part of last century. Improved application of established primary prevention strategies undoubtedly has the potential to further reduce the incidence of CAD. The exact mechanism linking genetic variation at 9p21 to the risk of CAD remains uncertain, although several sets of observations at the population level and in the laboratory have helped to point to the possibilities. Firstly, exactly same variants have been linked to extra cardiac atherosclerosis like carotid plaque, ischemic stroke, and peripheral arterial disease,suggesting that the locus predisposes to atherosclerosis in all vascular beds. Secondly, same variants have been linked to both19 abdominal aortic and intracranial arterial aneurysms, implying that the cells that are affected are in the vessel wall of the artery.Thirdly, evidence suggests that the SNPs in the high-risk region disrupt or create transcription factor binding sites that alter the expression levels, or the relative abundance of different transcripts of the non-coding ribonucleic acid, ANRIL, which in turn affects the expression levels of CDKN2B and/or 2A. The protein products of these 2 genes, p15INK4a and p16 INK4a, then alter the function of macrophages and/or vascular smooth muscle cells, facilitating the formation of atherosclerotic plaque. Fourthly,animal model studies suggest that these effects could involve increased proliferation and reduced apoptosis of resident 19 macrophages and/or vascular smooth muscle cells. To conclude, we are entering a new exciting era as we can use genetic risk variants for the prevention and management of coronary artery disease (CAD). Current knowledge pertaining to 60 susceptibility loci identified for CAD confirms the importance of established risk factors and many novel causal pathways. This will surely improve our understanding of genetic basis of CAD and hopefully open the door to development of new therapeutic agents in the future. Mendelian randomization studies have enhanced our understanding of causal relationship between CAD-related traits. This has further highlighted the potential benefits of long-term modifications of risk factors. Genetic risk scores of CAD are important both as prognostic and predictive markers. This may also change the approach to delivery of established prevention strategies.

Article: Review Article

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