Loss of heterozygosity on chromosomes 1, 2, 8, 9 and 17 in cerebral atherosclerotic plaques

Objective. Atherosclerosis is a fibroproliferative disease which has been a ttributed to several factors including genetic and molecular alterations. I nitial studies have shown genetic alterations at the microsatellite level i n the DNA of atherosclerotic plaques. Extending our initial findings, we pe rformed a microsatellite analysis on cerebral atherosclerotic plaques. Methods. Twenty-seven cerebral atherosclerotic plaques were assessed for lo ss of heterozygosity (LOH) and microsatellite instability (MI) using 25 mic rosatellite markers located on chromosomes 2, 8, 9 and 17. DNA was extracte d from the vessels as well as the respective blood from each patient and su bjected to polymerase chain reaction. Results. Our analyses revealed that specific loci on chromosomes 2, 8, 9 an d 17 exhibited a significant incidence of LOH. Forty-six percent of the spe cimens 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 i ncidence was 39%, 31% and 27% at 17q21, 9q31-34 and 17p13, respectively. Ge netic alterations were detected at a higher rate as compared to the corresp onding 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 m utational rate on specific chromosomal loci, suggesting a potential implica tion of these regions in atherogenesis.