Aortic atherosclerosis in diabetes mellitus is associated with an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. No relation between the polymorphism and aortic collagen content.
An insertion(I)/deletion(D) polymorphism in the angiotensin I-converting enzyme (ACE) gene seems to be associated with clinical heart disease in patients with diabetes mellitus. It is not known whether increased atherosclerosis or other factors among individuals with certain ACE-gene subtypes form the basis for the increased prevalence of heart disease among these subjects. We measured, at autopsy, the extent of macroscopically visible aortic atherosclerosis in 22 diabetic and 39 non-diabetic subjects and determined the ACE-genotype of all individuals by the polymerase chain reaction. The percentage of aortic surface area covered with atherosclerotic lesions was 29 +/- 8 (n = 6), 71 +/- 7 (n = 9), and 65 +/- 7 (n = 5) in the II-, ID-, and DD-genotype subgroups, respectively, among diabetes patients (mean +/- SEM) (2 p < 0.01, when comparing values from the ID and DD groups to the II group). The values were 37 +/- 9 (n = 11), 40 +/- 5 (n = 14) and 37 +/- 6 (n = 11) in the II-, ID-, and DD-genotypes in the non-diabetic group. There were no differences in sex ratio or age in any of the ACE-gene subtypes. The previously described relationship between heart disease and the ACE-gene polymorphism in diabetes could thus be founded in an increased extent of atherosclerosis among patients with the ID- and DD-ACE-gene subtypes. Patients with diabetes have several alterations in the composition of the collagenous components in the arterial wall. We also analysed for associations between total collagen and type IV and type V collagen content in the aortic vessel wall and the ACE-gene subtypes. We were, however, not able to disclose correlations between the polymorphism and any of these parameters. In conclusion, our data show an association between the ACE-I/D polymorphism and the degree of aortic atherosclerosis in diabetes; however, we did not observe correlations between the polymorphism and data concerning arterial collagenous components.
Rasmussen
L M
LM
Laboratory for Molecular Pathology, University Institute of Pathology, University Hospital of Aarhus, Kommunehospitalet, Denmark.
Ledet
T
T
D000368:Aged; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001344:Autopsy / Q000706:statistics & numerical data; D003094:Collagen / Q000032:analysis; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence
D017931:DNA Primers; D003094:Collagen; D004247:DNA; D007703:Peptidyl-Dipeptidase A