Title :

Genetics of the thrombomodulin-endothelial cell protein c receptor system and the risk of early-onset ischemic stroke

Author(s) :

Cole, John W. [Auteur]
Xu, Huichun [Auteur]
Ryan, Kathleen [Auteur]
Jaworek, Thomas [Auteur]
Dueker, Nicole [Auteur]
Mcardle, Patrick F. [Auteur]
Gaynor, Brady [Auteur]
Cheng, Yu-Ching [Auteur]
O''connell, Jeff [Auteur]
Bevan, Steve [Auteur]
Malik, Rainer [Auteur]
Ahmed, Naveed Uddin [Auteur]
Amouyel, Philippe [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Anjum, Sheraz [Auteur]
Bis, Joshua C. [Auteur]
Crosslin, David [Auteur]
Danesh, John [Auteur]
Engelter, Stefan T. [Auteur]
Fornage, Myriam [Auteur]
Frossard, Philippe [Auteur]
Gieger, Christian [Auteur]
Giese, Anne-Katrin [Auteur]
Grond-Ginsbach, Caspar [Auteur]
Ho, Weang Kee [Auteur]
Holliday, Elizabeth G. [Auteur]
Hopewell, Jemma C. [Auteur]
Hussain, M. [Auteur]
Iqbal, W. [Auteur]
Jabeen, S. [Auteur]
Jannes, Jim [Auteur]
Kamal, Ayeesha [Auteur]
Kamatani, Yoichiro [Auteur]
Kanse, Sandip M. [Auteur]
Kloss, Manja [Auteur]
Lathrop, Mark [Auteur]
LEYS, Didier [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV]
Lindgren, Arne G. [Auteur]
Longstreth, Will T. [Auteur]
Mahmood, Khalid [Auteur]
Meisinger, Christa [Auteur]
Metso, Tiina M. [Auteur]
Mosley, Thomas H. [Auteur]
Muller-Nurasyid, Martina [Auteur]
Norrving, Bo [Auteur]
Parati, Eugenio A. [Auteur]
Peters, Annette [Auteur]
Pezzini, Alessandro [Auteur]
Quereshi, I. [Auteur]
Rasheed, Asif [Auteur]
Rauf, A. [Auteur]
Salam, T. [Auteur]
Shen, Jess [Auteur]
Slowik, Agnieszka [Auteur]
Stanne, Tara M. [Auteur]
Strauch, Konstantin [Auteur]
Tatlisumak, Turgut [Auteur]
Thijs, Vincent N. S. [Auteur]
Tiedt, Steffen [Auteur]
Traylor, Matthew [Auteur]
Waldenberger, Melanie [Auteur]
Walters, Matthew R. [Auteur]
Zhao, Wei [Auteur]
Boncoraglio, Giorgio B. [Auteur]
Debette, Stéphanie [Auteur]
Jern, Christina [Auteur]
Levi, Christopher R. [Auteur]
Markus, Hugh S. [Auteur]
Meschia, James F. [Auteur]
Rolfs, Arndt [Auteur]
Rothwell, Peter M. [Auteur]
Saleheen, Danish [Auteur]
Seshadri, Sudha [Auteur]
Sharma, Pankaj [Auteur]
Sudlow, Cathie L. M. [Auteur]
Worrall, Bradford B. [Auteur]
Stine, O Colin [Auteur]
Kittner, Steven J. [Auteur]
Mitchell, Braxton D. [Auteur]

Journal title :

PLoS One

Abbreviated title :

PLoS ONE

Volume number :

13

Pages :

e0206554

Publication date :

2018-01-01

ISSN :

1932-6203

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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 multi-stage design of discovery and replication. 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 (onset-age<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. 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 additive-model 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. PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Submission date :

2019-11-27T14:35:17Z