Association of a single nucleotide polymorphism of the NPR3 gene promoter with early onset ischemic stroke in an Italian cohort |
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| Authors: | Speranza Rubattu Betti Giusti Luca Andrea Lotta Flora Peyvandi Maria Cotugno Rosita Stanzione Simona Marchitti Anna Maria Palombella Sara Di Castro Maurizia Rasura Pier Mannuccio Mannucci Massimo Volpe |
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| Affiliation: | 1. Department of Cardiology, School of Medicine and Psychology, Sapienza University, S. Andrea Hospital, Rome, Italy;2. IRCCS Neuromed, Pozzilli (Is), Italy;3. Department of Medical and Surgical Critical Care, Atherothrombotic Disease Unit, University of Florence, Careggi Hospital, Florence, Italy;4. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center U.O.S. Dipartimentale per la Diagnosi e la Terapia delle Coagulopatie, Fondazione IRCCS, Fondazione IRCCS Ca'' Granda Maggiore Policlinico Hospital Foundation and Luigi Villa Foundation, Milan, Italy;5. Stroke Unit, School of Medicine and Psychology, Sapienza University, S. Andrea Hospital, Rome, Italy;6. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Scientific Direction, IRCCS Ca'' Granda Maggiore Policlinico Hospital Foundation and Luigi Villa Foundation, Milan, Italy;1. Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan;2. Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan;3. Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan;1. Association for Cardiac Research — Associazione per la Ricerca Cardiologica, Rome, Italy;2. Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatrical Sciences, Sapienza University of Rome, Rome, Italy;3. Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, Rome, Italy;4. Department of Neurosciences, Human Nutrition Section, University of Rome Tor Vergata, Rome, Italy;1. Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan;2. Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan;1. Mario Negri Institute for Pharmacological Research, Milan, Italy;2. Dipartimento di Scienze Cliniche e di Comunità, IRCCS Maggiore Hospital Foundation, Milan, Italy;3. Internal Medicine I, Policlinico IRCCS San Donato, University of Milan, Italy;4. Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Italy;5. Geriatric Unit, Spedali Civili, Department of Medical and Surgery Sciences, University of Brescia, Italy;6. Department of Internal Medicine, University of Perugia, Italy;7. Scientific Direction, IRCCS Maggiore Hospital Foundation, Milan, Italy |
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| Abstract: | BackgroundNPR3, located on human chromosome 5 (5p14–p13), encodes the natriuretic peptide receptor type C (NPR-C) that is mainly known as the natriuretic peptide clearance receptor. Involvement of NPR3 in susceptibility to cardiovascular diseases, i.e. hypertension, has been previously shown. With regard to stroke predisposition, evidence for a potential role of genetic variation within or nearby NPR3 has been suggested by a previous genome wide association study.MethodsWe investigated the contribution to early-onset ischemic stroke susceptibility of the NPR3 ? 55 C > A transition by genotyping this variant in an Italian cohort of 368 cases and 335 controls.ResultsIn a multivariable logistic regression analysis adjusting for age, gender, hypertension, hypercholesterolemia, smoking habit and diabetes, a significant association of the ? 55 AA genotype with stroke was observed (OR = 3.2, 95% CI 1.2–8.3, p = 0.016). Remarkably, the polymorphism remained associated with stroke after adjusting for hypertensive status.ConclusionOur observation obtained in an Italian cohort of early onset ischemic strokes suggests that a NPR3 promoter gene variant could have a role on cerebrovascular disease susceptibility. |
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