Current status of understanding of the genetic etiology of coronary heart disease

Coronary heart disease (CHD), synonymously known as coronary artery disease (CAD) is the most predominant among the cardiovascular diseases and ranked number one in prevalence among the developing countries. CHD is a multifactorial disease involving both genetic and environmental factors and is primarily caused due to a process of progressive damage of coronary arteries called atherosclerosis. We present here a comprehensive review of molecular genetic studies conducted so far on CAD. The information was gathered through the internet using appropriate search terms for CHD/CAD. We also compiled the relevant information from the following websites: http://www.bioguo.org/CADgene/ and http://www.genome.gov. Besides several Mendelian forms of the CHD, ~300 more genes have been identified in different studies through candidate gene approach. Additionally 32 more loci have been identified through genome wide association studies that include 9p21.3 as the most replicated genetic locus across the globe. Nevertheless, overall, these studies have been characterized by a relative lack of consistency in the association pattern across the populations. A fair degree of ethnic variation in the nature of association of different genetic variants with the disease has also been apparent. Pleiotropic effects of genes, existence of subclinical phenotypes and genetic heterogeneity appear to have been the limiting factors for developing a genetic risk profile test for the disease. Given the high prevalence of this disease in India, the presence of environmental triggers and genetic variation, it would be prudent to conduct multi-ethnic large-scale studies in India, representing the subcontinent as a whole-there have been a very limited number of molecular genetic studies on Indian populations.