Abstract
To determine if genetic and environmental (dietary) factors and gene-environment interaction impact on the expression variation of genes related to stroke, we conducted microarray experiments using two homozygous rat strains SHRSR and SHRSP fed with high and low dietary salt levels. We obtained expression data of 8,779 genes and performed the ranking analysis of microarray data. The results show that the genetic difference for stroke in rat brain has a strong effect on expression variations of genes. At false discovery rate (FDR) ≤ 5%, 534 genes were found to be differentially expressed between the genotypes resistant and prone to stroke, among which 304 genes were up-regulated in the resistant genotype and down-regulated in the prone genotype and 230 were down-regulated in the former and up-regulated in the latter. In addition, 365 were functional genes for transcription and translation, receptors (in particular, neurotransmitter receptor), channels of ions, transportation, metabolism and enzymes, and functional and structural proteins. Some of these genes are pivotal genes that cause stroke. However, dietary salt levels and GE interaction do not strongly impact on the expression variations of these genes detected on arrays.
Highlights
Stroke is a major cause of severe disability and the third leading cause of death in the world
The genetic difference between genotypes results in the significant expression variations of genes related to stroke (Figure 1)
At false discovery rate (FDR) ≤ 5%, we found 341 functional genes differentially expressed between the genotypes SHRSP and SHRSR
Summary
Stroke is a major cause of severe disability and the third leading cause of death in the world. Stroke occurrence is a complex biological process involving obstruction of blood flow in a major cerebral vessel which leads to deregulation of genes whose expression promotes ischemic neuronal death and subsequent neurological dysfunction [1,2,3]. The development of stroke in an individual is influenced by a number of cardiovascular risk factors including genetic predispositions, hypertension, smoking, diabetes mellitus [4] as well as by dietary salt. The importance of genetic factor for stroke etiology has been documented by several rare monogenic diseases such CADASIL (cerebral autosomal dominant ateriopathy with subcortical infarcts and leukoencenphalopathy) and the genetic behavior of some genes for stroke [5,6,7,8,9,10]. G-50T in genes cytochrome P450 2J2 (CYP2J2) [4], G860A in a soluble epoxide hydrolase (EPHX2) [4], and plasma IL6 and CRP levels [13] were found to be significantly associated with risk of ischemic stroke
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