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Pechlaner, R.* ; Willeit, P.* ; Summerer, M.* ; Santer, P. ; Egger, G.* ; Kronenberg, F.* ; Demetz, E.* ; Weiss, G.* ; Tsimikas, S.* ; Witztum, J.L.* ; Willeit, K.* ; Iglseder, B.* ; Paulweber, B.* ; Kedenko, L.* ; Haun, M.* ; Meisinger, C. ; Gieger, C. ; Müller-Nurasyid, M. ; Peters, A. ; Willeit, J.* ; Kiechl, S.*

Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease.

Arterioscler. Thromb. Vasc. Biol. 35, 229-236 (2015)
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OBJECTIVE: The enzyme heme oxygenase-1 (HO-1) exerts cytoprotective effects in response to various cellular stressors. A variable number tandem repeat polymorphism in the HO-1 gene promoter region has previously been linked to cardiovascular disease. We examined this association prospectively in the general population. APPROACH AND RESULTS: Incidence of stroke, myocardial infarction, or vascular death was registered between 1995 and 2010 in 812 participants of the Bruneck Study aged 45 to 84 years (49.4% males). Carotid atherosclerosis progression was quantified by high-resolution ultrasound. HO-1 variable number tandem repeat length was determined by polymerase chain reaction. Subjects with ≥32 tandem repeats on both HO-1 alleles compared with the rest of the population (recessive trait) featured substantially increased cardiovascular disease risk (hazard ratio [95% confidence interval], 5.45 [2.39, 12.42]; P<0.0001), enhanced atherosclerosis progression (median difference in atherosclerosis score [interquartile range], 2.1 [0.8, 5.6] versus 0.0 [0.0, 2.2] mm; P=0.0012), and a trend toward higher levels of oxidized phospholipids on apolipoprotein B-100 (median oxidized phospholipids/apolipoprotein B level [interquartile range], 11364 [4160, 18330] versus 4844 [3174, 12284] relative light units; P=0.0554). Increased cardiovascular disease risk in those homozygous for ≥32 repeats was also detected in a pooled analysis of 7848 participants of the Bruneck, SAPHIR, and KORA prospective studies (hazard ratio [95% confidence interval], 3.26 [1.50, 7.33]; P=0.0043). CONCLUSIONS: This study found a strong association between the HO-1 variable number tandem repeat polymorphism and cardiovascular disease risk confined to subjects with a high number of repeats on both HO-1 alleles and provides evidence for accelerated atherogenesis and decreased antioxidant defense in this vascular high-risk group.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genetic Polymorphism ; Risk Factor
ISSN (print) / ISBN 1079-5642
e-ISSN 1524-4636
Quellenangaben Volume: 35, Issue: 1, Pages: 229-236 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Reviewing status Peer reviewed