ArticleArteriosclerosis, thrombosis, and vascular biology2015
Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease.
Open access · greenAbstract read
In one paragraph
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 9% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease.International journal of environmental research and public health · 2021Pooled it
- Pooled it
- Sex-Specific Association between HO-1 (GT)n Promoter Polymorphism and Large-Artery Atherosclerosis Stroke.Journal of atherosclerosis and thrombosis · 2025Article
- Heme oxygenase-1 polymorphisms associate with ischemic cardiac complications and all-cause mortality in type 1 diabetes.Cardiovascular diabetology · 2025Article
- Association between microsatellite polymorphism in the Heme Oxygenase-1 (HMOX1) gene promoter and type 2 diabetes: an updated meta-analysis.Journal of diabetes and metabolic disorders · 2025Review
- Heme Oxygenase-1 Gene (GT)n Polymorphism Linked to Deep White Matter Hyperintensities, Not Periventricular Hyperintensities.Journal of the American Heart Association · 2024Article
- Oxidized phospholipids in cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Molecular profiling of the stroke-induced alterations in the cerebral microvasculature reveals promising therapeutic candidates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review.Antioxidants (Basel, Switzerland) · 2022Review
- Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders.Antioxidants (Basel, Switzerland) · 2022Review
- Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.Pharmacology & therapeutics · 2022Review
- Integrated Bioinformatics-Based Identification of Ferroptosis-Related Genes in Carotid Atherosclerosis.Disease markers · 2022Article
- Association between HO‑1 gene promoter polymorphisms and diseases (Review).Molecular medicine reports · 2022Review
- Human gene polymorphisms and their possible impact on the clinical outcome of SARS-CoV-2 infection.Archives of virology · 2021Review
- Subjects with coronary artery disease and reduced ejection fraction have longer (GT)Heart and vessels · 2021Article
- Review
- Decreased Mortality Rate Among COVID-19 Patients Prescribed Statins: Data From Electronic Health Records in the US.Frontiers in medicine · 2021Article
- Heme oxygenase-1 modulation: A potential therapeutic target for COVID-19 and associated complications.Free radical biology & medicine · 2020Review
- Genetic Polymorphisms Complicate COVID-19 Therapy: Pivotal Role of HO-1 in Cytokine Storm.Antioxidants (Basel, Switzerland) · 2020Review
- Association of heme oxygenase-1 single nucleotide polymorphisms with susceptibility to tuberculosis in Chinese Han population.Journal of clinical laboratory analysis · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 8 institutions in 5 countries.
Raimund PechlanerFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Peter WilleitFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Monika SummererFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Peter SanterFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Georg EggerFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Florian KronenbergFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Egon DemetzFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Günter WeissFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Sotirios TsimikasFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Joseph L WitztumFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Karin WilleitFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Bernhard IglsederFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Bernhard PaulweberFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Lyudmyla KedenkoFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Margot HaunFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Christa MeisingerFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Christian GiegerFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Martina Müller-NurasyidFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Annette PetersFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Johann WilleitFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.).
Stefan KiechlFrom the Department of Neurology (R.P., P.W., K.W., J.W., S.K.) and Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology (M.S., F.K., M.H.), Medical University of Innsbruck, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.); Departments of Laboratory Medicine (P.S.) and Internal Medicine (G.E.), Hospital of Bruneck, Bruneck, Italy; Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria (E.D., G.W.); Department of Medicine, University of California San Diego, La Jolla (S.T., J.L.W.); Department of Geriatric Medicine (B.I.) and First Department of Internal Medicine (B.P., L.K.), Paracelsus Medical University/Salzburger Landeskliniken, Salzburg, Austria; Institute of Epidemiology II (C.M., A.P.), Institute of Genetic Epidemiology (C.G., M.M.-N.), Research Unit of Molecular Epidemiology (C.G.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany (M.M.-N.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (M.M.-N., A.P.). stefan.kiechl@i-med.ac.at.
University of California, San Diego · USKrankenhaus Bruneck · ITLudwig-Maximilians-Universität München · DEParacelsus Medical University · ATInnsbruck Medical University · ATSalzburger Landeskliniken · ATUniversität Innsbruck · ATUniversity of Cambridge · GB
Funding
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4MSCOR IN MOLECULAR MEDICINE AND ATHEROSCLEROSISP50HL056989 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI QUEHENBERGER, OSWALD · 1997 to 2006
$14.1MOxidation-specific nanoparticles for imaging atherosclerosisR01HL119828 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TSIMIKAS, SOTIRIOS · 2013 to 2017
$2.0MAustrian Science Fund FWF TRP 188NHLBI NIH HHS HL 088093NHLBI NIH HHS HL 119828NHLBI NIH HHS P01 HL088093NHLBI NIH HHS P50 HL056989
Abstract
objectiveThe 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
resultsIncidence 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).
conclusionsThis 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.
Indexed as
Minisatellite RepeatsPolymorphism, GeneticPromoter Regions, GeneticAgedAged, 80 and overApolipoprotein B-100AtherosclerosisAustriaCardiovascular DiseasesDisease ProgressionFemaleGenetic MarkersGenetic Predisposition to DiseaseHeme Oxygenase-1HeterozygoteHomozygoteAPOB protein, humanApolipoprotein B-100Genetic MarkersHeme Oxygenase-1HMOX1 protein, humanPhospholipidsatherosclerosiscardiovascular diseasegenetic polymorphismrisk factor
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