Precision medicine considerations for the management of heart disease and stroke in East Asians

Heart disease is the leading cause of death in Asian Americans. Importantly, people of East Asian descent are more likely to carry a loss-of-function point mutation in aldehyde dehydrogenase 2 (ALDH2), ALDH2*2, which reduces ALDH2 enzymatic activity by at least 40% relative to wild type ALDH2. Given the role of ALDH2 in removing toxic aldehydes from the cell, ALDH2 is intimately involved in the cardioprotective mechanisms of ischemic preconditioning and the pathophysiology of ischemia reperfusion injury. The ALDH2*2 variant is associated with an increased incidence of coronary artery disease, myocardial infarction, and stroke. Furthermore, this variant is associated with insensitivity to nitroglycerin, which is commonly prescribed in patients with cardiovascular disease. In this review, we discuss the genetic susceptibility and pathophysiology associated with the ALDH2*2 variant in regards to cardiovascular disease. We also present the considerations for the management of heart disease and stroke specific to East Asians carrying the ALDH2*2 genetic variant.