Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm.
OBJECTIVE
Vascular inflammation is a hallmark in the development of abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a novel vascular anti-inflammatory factor. A (GT)(n) dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates the level of gene transcription. Short (< 25 GT) repeats are associated with an increased HO-1 upregulation in response to inflammatory stimuli than are longer repeats. We hypothesised that patients with AAA had less frequently short repeats in the HO-1 gene promoter compared to patients with coronary (CAD) or peripheral artery disease (PAD), or healthy controls.


METHODS
70 consecutive patients with atherosclerotic AAA, each 70 age- and sex-matched patients with CAD and PAD as well as 61 unmatched healthy atherosclerosis-free controls for a total of 271 individuals were studied. The frequency of carriers of short repeats in the HO-1 gene promoter was determined and compared between the groups.


RESULTS
In the AAA group, 29 patients (41%) were carriers of short (GT)(n) repeats compared to 47 patients (67%) in the CAD group, 44 patients (63%) in the PAD group and 35 healthy controls (59%). Patients with AAA were less frequently carriers of short repeats compared to age- and sex-matched patients with CAD (OR = 0.38, p = 0.006) and PAD (OR = 0.35, p = 0.01). Healthy controls exhibited short alleles more frequently than patients with AAA (p = 0.04), but comparable to CAD (p = 0.3) and PAD patients (p = 0.7).


CONCLUSIONS
Patients with AAA were less frequently carriers of short (< 25 GT) repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy subjects. This suggests that short alleles, and thus, facilitated upregulation of HO-1, may be a protective anti-inflammatory factor against the development of AAA.
Schillinger
Martin
M
Division of Angiology, Department of Internal Medicine II, University of Vienna, Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. martin.schillinger@akh-wien.ac.at
Exner
Markus
M
Mlekusch
Wolfgang
W
Domanovits
Hans
H
Huber
Kurt
K
Mannhalter
Christine
C
Wagner
Oswald
O
Minar
Erich
E
D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000235:genetics*; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D018598:Minisatellite Repeats; D016491:Peripheral Vascular Diseases / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1