This study showed that the ALDH2 rs671 variant, present in 30-50% of East Asians, enhances platelet activation and arterial thrombosis, explaining the increased MI risk in carriers of this common genetic polymorphism.
BACKGROUND:Acute myocardial infarction caused by thrombosis is a major cause of mortality. A polymorphism in aldehyde dehydrogenase 2 (Aldh2) rs671 is found in approximately 30% to 50% of East Asians, and it is a risk factor for acute myocardial infarction. This mutation impairs ALDH2 function, but the effect of ALDH2 on platelet activation and thrombosis is unknown.METHODS:Platelets were isolated from platelet-specificAldh2−/−mice and ALDH2E506Kknockin mice (which correspond to the humanAldh2rs671 gene mutation) as well as from healthy human donors withAldh2rs671. Arterial thrombosis was measured in a ferric chloride (FeCl3)-induced thrombosis mouse model. The efficacy of Alda-1, an ALDH2 activator, in mitigating thrombogenesis was measured in ALDH2E506Kmice. Using a murine model of myocardial infarction, we analyzed the effects of plateletAldh2on microthrombosis and infarct expansion post myocardial infarction. In addition, we enrolled 118 patients of differentAldh2rs671 genotypes (G
