Genomic rearrangements on VCAM1, SELE, APEG1and AIF1 loci in atherosclerosis.
The inflammatory nature of atherosclerosis has been well established. However, the initial steps that trigger this response in the arterial intima remain obscure. Previous studies reported a significant rate of genomic alterations in human atheromas. The accumulation of genomic rearrangements in vascular endothelium and smooth muscle cells may be important for disease development. To address this issue, 78 post-mortem obtained aortic atheromas were screened for microsatellite DNA alterations versus correspondent venous blood. To evaluate the significance of these observations, 33 additional histologically normal aortic specimens from age and sex-matched cases were examined. Loss of heterozygosity (LOH) was found in 47,4% of the cases and in 18,2% of controls in at least one locus. The LOH occurrence in aortic tissue is associated to atherosclerosis risk (OR 4,06, 95% CI 1,50 to 10,93). Significant genomic alterations were found on 1p32-p31, 1q22-q25, 2q35 and 6p21.3 where VCAM1, SELE, APEG1 and AIF1 genes have been mapped respectively. Our data implicate somatic DNA rearrangements, on loci associated to leukocyte adhesion, vascular smooth muscle cells growth, differentiation and migration, to atherosclerosis development as an inflammatory condition.
Arvanitis
D A
DA
Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
Flouris
G A
GA
Spandidos
D A
DA
D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics*; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008840:Microfilament Proteins; D018895:Microsatellite Repeats; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D016017:Odds Ratio; D017346:Protein Serine-Threonine Kinases; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D019040:E-Selectin; D005819:Genetic Markers; D008840:Microfilament Proteins; D009124:Muscle Proteins; D019010:Vascular Cell Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; C100675:SPEG protein, human