17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status
| Autor: | Muhammed Saleem Khan, Emilio Ciusani, Alessandro Biffi, Helen Segal, Poneh Adib-Samii, Karen L. Furie, Myriam Fornage, Kaitlin Fitzpatrick, Hugh S. Markus, Peter M. Rothwell, Braxton D. Mitchell, Eugenio Parati, Martin Dichgans, Valerie Valant, S. J. Kittner, Benison C. Lau, Natalia S. Rost, Dale M Gamble, William J. Devan, Alexa Richie, Rainer Malik, Steve Bevan, Cathie Sudlow, Yu-Ching Cheng, Allison Kanakis, Carlos Leiva-Salinas, Silvia Lanfranconi, Joshua C. Bis, Bradford B. Worrall, Pankaj Sharma, Will Longstreth, Joanna M. Wardlaw, Thomas H. Mosley, Kerri L. Wiggins, Andreas Gschwendtner, Christopher Levi, Jonathan Rosand, Guido J. Falcone, Jane Maguire, Bruce M. Psaty, Elizabeth G. Holliday, Matthew Traylor, James F. Meschia, Giorgio B. Boncoraglio |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology Lacunar stroke Genotype Locus (genetics) Genome-wide association study Nerve Fibers Myelinated Polymorphism Single Nucleotide Article Internal medicine Humans Medicine cardiovascular diseases Aged Aged 80 and over Advanced and Specialized Nursing Neurology & Neurosurgery medicine.diagnostic_test business.industry Case-control study Leukoaraiosis Brain Magnetic resonance imaging Middle Aged medicine.disease Magnetic Resonance Imaging Hyperintensity Stroke Case-Control Studies Stroke Lacunar Ischemic stroke Linear Models Cardiology Female Neurology (clinical) Cardiology and Cardiovascular Medicine business Chromosomes Human Pair 17 Genome-Wide Association Study |
| Zdroj: | Stroke. 44:1609-1615 |
| ISSN: | 1524-4628 0039-2499 |
| Popis: | Background and Purpose— Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods— We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results— Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 ( P =0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions— This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction. |
| Databáze: | OpenAIRE |
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