Abstract
Coronary artery disease (CAD), including myocardial infarction (MI), is a common complex disease caused by atherosclerosis. Although more than 50 genetic variants have been associated with CAD, these loci collectively account for only 10% of CAD cases. Genetic variants of low and rare frequencies have been proposed as the main causes of CAD. SIRT6, one of the highly conserved NAD-dependent class III deacetylases, has been implicated in cardiovascular diseases. Considering the important roles that SIRT6 plays in the cardiovascular system, inflammation, and lipid and cholesterol metabolism, genetic variants were hypothesized to contribute to MI development. The promoter regions of the SIRT6 gene were genetically analyzed in large cohorts of MI patients (n = 371) and ethnically-matched controls (n = 383). A total of 15 DNA sequence variants (DSVs) were identified, including seven single-nucleotide polymorphisms (SNPs). Two novel heterozygous DSVs, g.4183823G>C and g.4183742G>A, were identified in two MI patients but in none of the controls. Two SNPs, g.4183685T>C (rs4359565) and g.4182942C>A (rs3760905), were found in MI patients with significantly higher frequencies compared with controls. These DSVs identified in MI patients may alter the transcriptional activity of the SIRT6 gene promoter and alter SIRT6 levels which might contribute to the risk of MI.
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