Aim: HDAC9 is a class IIa histone deacetylase family member and it regulates the epigenetic status of histones and therefore gene expression by catalyzing deacetylation. Risk variant rs11984041 of HDAC9 gene has been demonstrated to be associated with large vessels stroke. HDAC9 expression has been correlated with common carotid intima-media thickness, suggesting an association of HDAC9 gene with the atherosclerotic process, by accelerating atherosclerosis or promoting plaque instability. In this study we investigated the expression of HDAC9 in peripheral blood (PB) of stroke patients (large vessel and cardioembolic) and healthy controls. Aiming to understand the mechanism by which the risk allele is associated with large vessel stroke, we also evaluate the effect of rs11984041 polymorphism on gene expression. Methods: HDAC9 gene expression analysis was performed on 26 atherothrombotic stroke patients, 26 cardioembolic stroke patients, and 20 healthy controls by Real Time PCR using Sybr Green. Polymorphism rs11984041 was genotyped by PCR-RFLP method. Results: A significant increase of HDAC9 gene expression was observed in atherothrombotic and cardioembolic stroke patients compared to healthy controls (1.39±0.68 vs 0.61±0.36; p<0.001; 1.58±1.19 vs 0.60±0.36; p<0.001, respectively). The genotyping of 70 individuals showed no gene expression differences between patients carrying CC and CT genotypes. Conclusions: The gene HDAC9 is overexpressed in stroke patients compared to controls. This result indicated that this gene, that can regulate other genes implicated in the peripheral inflammatory reaction after stroke can represent a new target for the development of therapeutic agents against ischemic stroke injury.
HDAC9 gene is overexpressed in stroke patients
FERRONATO, Silvia;OLIVATO, Silvia;SCURO, Alberto;PATUZZO, Cristina;MAZZUCCO, Sara;GOMEZ, Maria Macarena
2014-01-01
Abstract
Aim: HDAC9 is a class IIa histone deacetylase family member and it regulates the epigenetic status of histones and therefore gene expression by catalyzing deacetylation. Risk variant rs11984041 of HDAC9 gene has been demonstrated to be associated with large vessels stroke. HDAC9 expression has been correlated with common carotid intima-media thickness, suggesting an association of HDAC9 gene with the atherosclerotic process, by accelerating atherosclerosis or promoting plaque instability. In this study we investigated the expression of HDAC9 in peripheral blood (PB) of stroke patients (large vessel and cardioembolic) and healthy controls. Aiming to understand the mechanism by which the risk allele is associated with large vessel stroke, we also evaluate the effect of rs11984041 polymorphism on gene expression. Methods: HDAC9 gene expression analysis was performed on 26 atherothrombotic stroke patients, 26 cardioembolic stroke patients, and 20 healthy controls by Real Time PCR using Sybr Green. Polymorphism rs11984041 was genotyped by PCR-RFLP method. Results: A significant increase of HDAC9 gene expression was observed in atherothrombotic and cardioembolic stroke patients compared to healthy controls (1.39±0.68 vs 0.61±0.36; p<0.001; 1.58±1.19 vs 0.60±0.36; p<0.001, respectively). The genotyping of 70 individuals showed no gene expression differences between patients carrying CC and CT genotypes. Conclusions: The gene HDAC9 is overexpressed in stroke patients compared to controls. This result indicated that this gene, that can regulate other genes implicated in the peripheral inflammatory reaction after stroke can represent a new target for the development of therapeutic agents against ischemic stroke injury.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.