Dataset Information

Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

ABSTRACT: Background and Purpose- Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods- Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed. Results- Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance (P<5×10^-8). The 14q24.3 locus was associated with acute stroke outcome (rs112809786, P=0.036) and with ACOT1 and PTGR2 gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study. Conclusions- We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.

SUBMITTER: Torres-Aguila NP

PROVIDER: S-EPMC6878188 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

Torres-Aguila Nuria P NP Carrera Caty C Giese Anne-Katrine AK Cullell Natalia N Muiño Elena E Cárcel-Márquez Jara J Gallego-Fabrega Cristina C González-Sánchez Jonathan J Del Mar Freijo María M Álvarez-Sabín José J Molina Carlos C Ribó Marc M Jimenez-Conde Jordi J Roquer Jaume J Sobrino Tomás T Campos Francisco F Castillo José J Muñoz-Narbona Lucia L Lopez-Cancio Elena E Dàvalos Antoni A Diaz-Navarro Rosa R Tur Silvia S Vives-Bauza Cristòfol C Serrano-Heras Gemma G Segura Tomás T Krupinski Jerzy J Delgado-Mederos Raquel R Martí-Fàbregas Joan J Heitsch Laura L Ibañez Laura L Cruchaga Carlos C Rost Natalia S NS Montaner Joan J Lee Jin-Moo JM Fernandez-Cadenas Israel I

Stroke 20191007 12

Background and Purpose- Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods- Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed. Results- Our genome-wide association study, which included 2064 (Discovery) and 407 (Repli ...[more]

PMID: 31587654

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Project description:IntroductionHigher white blood cell (WBC) count is associated with poor functional outcome in acute ischemic stroke (AIS). However, little is known about whether the association is modified by treatment with intravenous alteplase.MethodsWAKE-UP was a randomized controlled trial of the efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in unknown onset stroke. WBC count was measured on admission and again at 22-36 h after randomization to treatment (follow-up). Favorable outcome was defined by a score of 0 or 1 on the modified Rankin scale (mRS) 90 days after stroke. Further outcome were stroke volume and any hemorrhagic transformation (HT) that were assessed on follow-up CT or MRI. Multiple logistic regression analysis was used to assess the association between outcome and WBC count and treatment group.ResultsOf 503 randomized patients, WBC count and baseline parameters were available in 437 patients (μ = 64.7 years, 35.2% women) on admission and 355 patients (μ = 65.1 years, 34.1% women) on follow-up. Median WBC count on admission was 7.6 × 109/L (interquartile range, IQR, 6.1-9.4 × 109/L) and 8.2 × 109/L (IQR, 6.7-9.7 × 109/L) on follow-up. Higher WBC count both on admission and follow-up was associated with lower odds of favorable outcome, adjusted for age, National Institutes of Health (NIH) Stroke Scale Score, temperature, and treatment (alteplase vs. placebo, adjusted odds ratio, aOR 0.85, 95% confidence interval [CI] 0.78-0.94 and aOR 0.88, 95% CI 0.79-0.97). No interaction between WBC count and treatment group was observed (p = 0.11). Furthermore, WBC count on admission and follow-up was significantly associated with HT (aOR 1.14, 95% CI 1.05-1.24 and aOR 1.13, 95% CI 1.00-1.26). Finally, WBC count on follow-up was associated with larger stroke volume (aOR 2.57, 95% CI 1.08-6.07).ConclusionHigher WBC count is associated with unfavorable outcome, an increased risk of HT, and larger stroke volume, independent of treatment with alteplase. Whether immunomodulatory manipulation of WBC count improves stroke outcome needs to be tested.Trial registrationClinicalTrials.gov Identifier: NCT01525290.

Dataset Information

Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

Publications

Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke.

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