دورية أكاديمية
Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke
| العنوان: | Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke |
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| المؤلفون: | Cole, J.W., Xu, H., Ryan, K. |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2018 |
| المجموعة: | UMB Digital Archive (University of Maryland, Baltimore) |
| مصطلحات موضوعية: | brain ischemia, gene linkage disequilibrium |
| الوصف: | Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multistage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r2-0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onsetage< 60 years) consisting of 3676 cases and 21118 non-stroke controls from 6 case-control studies. Lastly, we determined if the replicated SNPs also associated with older-onset ischemic stroke in the METASTROKE data-base. Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additivemodel adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | PLoS ONE; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055915276&doi=10.1371%2fjournal.pone.0206554&partnerID=40&md5=5d4ae559784e89eafc57f5e769417672Test; http://hdl.handle.net/10713/9792Test |
| DOI: | 10.1371/journal.pone.0206554 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0206554Test http://hdl.handle.net/10713/9792Test |
| رقم الانضمام: | edsbas.E9E5FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0206554 |
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