Genetic variation contributes to gene expression response in ischemic stroke: an eQTL study

Abstract

Objective Single nucleotide polymorphisms (SNPs) contribute to complex disorders such as ischemic stroke (IS). Since SNPs could affect IS by altering gene expression, we studied the association of common SNPs with changes in mRNA expression (i.e. expression quantitative trait loci; eQTL) in blood after IS. Methods RNA and DNA were isolated from 137 patients with acute IS and 138 vascular risk factor controls (VRFC). Gene expression was measured using Affymetrix HTA 2.0 microarrays and SNP variants were assessed with Axiom Biobank Genotyping microarrays. A linear model with a genotype (SNP) × diagnosis (IS and VRFC) interaction term was fit for each SNP‐gene pair. Results The eQTL interaction analysis revealed significant genotype × diagnosis interaction for four SNP‐gene pairs as cis‐eQTL and 70 SNP‐gene pairs as trans‐eQTL. Cis‐eQTL involved in the inflammatory response to IS included rs56348411 which correlated with neurogranin expression (NRGN), rs78046578 which correlated with CXCL10 expression, rs975903 which correlated with SMAD4 expression, and rs62299879 which correlated with CD38 expression. These four genes are important in regulating inflammatory response and BBB stabilization. SNP rs148791848 was a strong trans‐eQTL for anosmin‐1 (ANOS1) which is involved in neural cell adhesion and axonal migration and may be important after stroke. Interpretation This study highlights the contribution of genetic variation to regulating gene expression following IS. Specific inflammatory response to stroke is at least partially influenced by genetic variation. This has implications for progressing toward personalized treatment strategies. Additional research is required to investigate these genes as therapeutic targets.

The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population

“…Rs2980003 might be associated with the regulation of DNAse and NHGRI/EBI GWAS hits. Several studies provided increasing evidence to support that SNPs confer susceptibilities by affecting gene expression [43][44][45]. Thus, we hypothesized that CYP7B1 polymorphisms, especially rs6472155 and rs2980003 may affect the expression of CYP7B1 to contribute to the risk of CHD.…”

Peripheral Blood Gene Expression at 3 to 24 Hours Correlates with and Predicts 90-Day Outcome Following Human Ischemic Stroke

“…SMAD4 has been implicated in inflammation and hypercoagulation in ischemic stroke [60], has been associated with BBB disruption [61] and in our previous study was up-regulated in IS subjects who later developed hemorrhagic transformation [60]. We have previously observed higher expression of SMAD4 after IS, and particularly higher in individuals with the GG allele of rs975903 [62]. This could relate in part to post-translational regulation of SMAD proteins in response to TGF-β signaling [63].…”

Association between single-nucleotide polymorphism rs145497186 related to NDUFV2 and lumbar disc degeneration: a pilot case–control study

“…Accordingly, changes in the function of the proteins produced may occur. These changes may directly or indirectly affect normal physiological activities and contribute to disease [ 36 ]. Therefore, it is very meaningful to explore the relationship between disease and SNPs.…”