Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke
| Autor: | Michèle M. Sale, Andrew M. Southerland, Stephen R. Williams, Karen L. Furie, Godfrey Dzhivhuho, Bradford B. Worrall, Fang-Chi Hsu, Wei-Min Chen, Stephen S. Rich, Keith L. Keene, Joe L. Rowles |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Risk 0301 basic medicine congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Quantitative Trait Loci Population Gene Expression Genome-wide association study Polymorphism Single Nucleotide Article Brain Ischemia Brain ischemia 03 medical and health sciences 0302 clinical medicine Von Willebrand factor Recurrence Recurrent stroke hemic and lymphatic diseases Internal medicine von Willebrand Factor Humans Medicine Thrombus education Aged Aged 80 and over Advanced and Specialized Nursing education.field_of_study biology business.industry Middle Aged medicine.disease Surgery Stroke 030104 developmental biology Ischemic stroke biology.protein Cardiology Female Neurology (clinical) Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery Genome-Wide Association Study circulatory and respiratory physiology |
| Zdroj: | Stroke. 48:1444-1450 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/strokeaha.116.015677 |
| Popis: | Background and Purpose— von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. Methods— We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors. We conducted a genome-wide association study) with imputation, based on 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus analysis for vWF across different tissues. Results— Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified single-nucleotide polymorphisms significantly associated with circulating vWF at the ABO locus ( P −8 ) and replicated findings from previous genetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated ABO single-nucleotide polymorphisms were also associated with vWF gene expression. Conclusions— Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk and may have implications for clinical care decision making. |
| Databáze: | OpenAIRE |
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