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Gene Expression Profiles at Early vs Late Stages After Cervical Artery Dissection
Robert B Ferguson1, Ilana E Green2, Timothy L Mcmurry3
1Department of Neurology, University of Virginia, Charlottesville.
Background And Objectives:
Cervical artery dissection (CeAD) is a common cause of stroke in young adults. While the pathogenesis of CeAD remains poorly understood, clinical and genetic associations suggest a systemic arteriopathy at the early phase of CeAD. We hypothesize that individuals experiencing CeAD express a distinct gene expression profile at the early phase compared with (1) age-matched and sex-matched controls and (2) late-phase profiles within the same individual at a later time point.
Methods:
We prospectively enrolled patients (n = 37) with CeAD with and without ischemic stroke (IS) from 2014 to 2016, excluding cases of significant trauma or known monogenic connective tissue disease. We compared CeAD cases with non-CeAD IS cases (n = 16) and healthy controls (n = 11). Study personnel collected blood samples within 4 weeks of the event and again at a 3-6-month follow-up. We assessed gene expression using microarray analysis at the time of CeAD, relative to controls and >3-month follow-up samples within CeAD cases. We applied a mixed-effects regression model that included covariates of age, sex, race/ethnicity, time of enrollment, and stroke occurrence. We used a false discovery rate (FDR) cutoff of 5% and a 1.5-fold change cutoff to identify robust differential expression.
Results:
Within early-phase CeAD cases, 1,238 genes showed differential expression at a 5% FDR compared with late-phase profiles, with 31 genes exhibiting at least a 1.5-fold change. We identified 538 differentially expressed genes between patients with CeAD and controls, of which 30 reached the 1.5-fold threshold. Comparison of late-phase profiles with controls revealed 11 differentially expressed genes. Gene ontology highlighted that 7 of the 11 genes were associated with hemoglobin metabolism.
Discussion:
In this preliminary gene expression analysis of patients with CeAD, we identified a distinct gene expression profile associated with early-phase dissection. The predominance of differential gene expression related to hemoglobin metabolism warrants further study and replication in independent cohorts of patients with arterial dissection.
