Functional genetic variants within the SIRT2 gene promoter in acute myocardial infarction.

ABSTRACT: Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the complication of atherosclerosis. Recently, genome-wide association studies have identified a large number of CAD-related genetic variants. However, only 10% of CAD cases could be explained. Low frequent and rare genetic variants have been recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family, NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy, as well as in platelet function. Thus, we hypothesized that genetic variants in SIRT2 gene may contribute to AMI. In this study, SIRT2 gene promoter was analyzed in large cohorts of AMI patients (n = 375) and ethnic-matched controls (n = 377). Three novel heterozygous DSVs (g.38900888_91delTAAA, g.38900270A>G and g.38899853C>T) were identified in three AMI patients, but in none of controls. These DSVs significantly altered the transcriptional activity of the SIRT2 gene promoter (P<0.05) in both HEK-293 and H9c2 cells. Five novel heterozygous DSVS (g.38900562C>T, g.38900413A>C, g.38900030G>A, g.38899925A>C and g.38899852C>T) were only found in controls, which did not significantly affected SIRT2 gene promoter activity (P>0.05). In addition, four novel heterozygous DSVs and five SNPs were found in both AMI patients and control with similar frequencies (P>0.05), two SNPs of which were examined and did not affect SIRT2 gene promoter activity (P>0.05). Taken together, the DSVs identified in AMI patients may change SIRT2 level by affecting the transcriptional activity of SIRT2 gene promoter, contributing to the AMI development as a rare risk factor.

SUBMITTER: Yang W 

PROVIDER: S-EPMC5406008 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature