Loss of Heterozygosity on Chromosomes 1,2,8,9 and 17 in Cerebral Atherosclerotic plaques

Abstract

Objective

Atherosclerosis is a fibroproliferative disease which has been attributed to several factors including genetic and molecular alterations. Initial studies have shown genetic alterations at the microsatellite level in the DNA of atherosclerotic plaques. Extending our initial findings, we performed a microsatellite analysis on cerebral atherosclerotic plaques.

Methods

Twenty-seven cerebral atherosclerotic plaques were assessed for loss of heterozygosity (LOH) and microsatellite instability (MI) using 25 microsatellite markers located on chromosomes 2, 8, 9 and 17. DNA was extracted from the vessels as well as the respective blood from each patient and subjected to polymerase chain reaction.

Results

Our analyses revealed that specific loci on chromosomes 2, 8, 9 and 17 exhibited a significant incidence of LOH. Forty-six percent of the specimens showed loss of heterozygosity at 2p13–p21, 48% exhibited LOH at 8p12–q11.2, while allelic imbalance was detected in 47% of the cases. The LOH incidence was 39%, 31% and 27% at 17q21, 9q31–34 and 17p13, respectively. Genetic alterations were detected at a higher rate as compared to the corresponding alterations observed in plaques from other vessels.

Discussion

This is the first microsatellite analysis using atherosclerotic plaques obtained from cerebral vessels. Our results indicate an elevated mutational rate on specific chromosomal loci, suggesting a potential implication of these regions in atherogenesis.