Open AccessGenomic rearrangements on VCAM1, SELE, APEG1 and AIF1 loci in atherosclerosis
Author(s) -
Arvanitis D. A.,
Flouris G. A.,
Spandidos D. A.
Publication year - 2005
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2005.tb00345.x
Subject(s) - loss of heterozygosity , biology , locus (genetics) , somatic cell , genetics , genomic dna , microsatellite , gene , pathology , medicine , allele
The inflammatory nature of atherosclerosis has been well established. However, the initial steps that trigger this reponse 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.