Genetics of carotid atherosclerosis

Cardiovascular disease and stroke are heterogeneous and multifactorial diseases. Given the extreme complexity of risk factors contributing to the complex diseases, evaluation of the intermediate phenotypes may be more advantageous than the solid clinical events. Carotid artery atherosclerosis can be assessed by intima-media thickness (IMT) that represents carotid artery structure and arterial distensibility which is an index for an arterial function. These intermediate phenotypes are also risk factors for stroke and cardiovascular events. Gene mapping studies have been conducted to identify susceptibility genes to IMT and/or distensibility. However, most genes could not be consistently replicated by subsequent studies. Among them, the APOE epsilon polymorphism and the ACE I/D polymorphism are most extensively studied. Meta-analysis indicated that the epsilon4 and D alleles are associated with increased IMT. With more feasibility to conduct whole genome association studies and the awareness of using a large sample size to confirm a genetic effect for common diseases, it is expected that more candidate genes will be confirmed and more novel genes will be identified in the near future.