Atherosclerotic Aortic Calcification-Associated Polymorphism in HDAC9 and Associations with Mortality, Cardiovascular Disease, and Kidney Disease

Histone deacetylase 9 (HDAC9) has recently been demonstrated as a key regulator of vascular smooth muscle cell (VSMC) phenotype and is associated with abdominal aortic calcification, myocardial infarction, and ischemic stroke. It is uncertain whether HDAC9 is also implicated in other VSMC-driven diseases. Our objective was to assess associations between abdominal aortic calcification-associated genetic variation in HDAC9 and VSMC-associated phenotypes. In this prospective population study of 335,146 adults enrolled in the UK Biobank, the abdominal aortic calcification-associated risk allele of a genetic variant in HDAC9 was associated with increased risk of systolic hypertension, non-ST segment elevation myocardial infarction, and ischemic stroke. There was a suggestive protective association with kidney disease outcomes that did not reach experiment-wise significance. These genetic results lend further support for HDAC9 as a potential therapeutic target for arterial stenotic and calcific disease.