Smoking affects gene expression in blood of patients with ischemic stroke.

Objective Though cigarette smoking (CS) is a well-known risk factor for ischemic stroke (IS), there is no data on how CS affects the blood transcriptome in IS patients. Methods We recruited IS-current smokers (IS-SM), IS-never smokers (IS-NSM), control-smokers (C-SM), and control-never smokers (C-NSM). mRNA expression was assessed on HTA-2.0 microarrays and unique as well as commonly expressed genes identified for IS-SM versus IS-NSM and C-SM versus C-NSM. Results One hundred and fifty-eight genes were differentially expressed in IS-SM versus IS-NSM; 100 genes were differentially expressed in C-SM versus C-NSM; and 10 genes were common to both IS-SM and C-SM (P < 0.01; |fold change| >= 1.2). Functional pathway analysis showed the 158 IS-SM-regulated genes were associated with T-cell receptor, cytokine-cytokine receptor, chemokine, adipocytokine, tight junction, Jak-STAT, ubiquitin-mediated proteolysis, and adherens junction signaling. IS-SM showed more altered genes and functional networks than C-SM. Interpretation We propose some of the 10 genes that are elevated in both IS-SM and C-SM (GRP15, LRRN3, CLDND1, ICOS, GCNT4, VPS13A, DAP3, SNORA54, HIST1H1D, and SCARNA6) might contribute to increased risk of stroke in current smokers, and some genes expressed by blood leukocytes and platelets after stroke in smokers might contribute to worse stroke outcomes that occur in smokers.