Genetic Aspects of Inflammation and Immune Response in Stroke

Abstract

Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of candidate genes, such as IL-6, BDNF, COX2, CYPC19, and GPIIIa could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in genesPATJ and LOC as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation.

Single-Nucleotide Polymorphisms in Oxidative Stress-Related Genes and the Risk of a Stroke in a Polish Population—A Preliminary Study

“…Ischemic stroke, the most common type of a stroke, is a complex multifactorial disease caused by the interaction between environmental risk factors and genetic predisposition [ 17 , 18 , 19 ]. To date, numerous case-control studies have confirmed the association between SNPs and a stroke [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Ischemic strokes occurring in the carotid circulation are the most common type of an ischemic stroke, accounting for approximately 85% of all cases [ 27 ].…”

Genetic and Epigenomic Modifiers of Diabetic Neuropathy

“…In individuals with DN, increased inflammatory cytokines as well as different levels of certain growth factors were observed [ 42 ]. However, it should be mentioned that the inflammation has a more complex role in DN pathogenesis, since it is not only involved in processes that results in nerve damage, but also in process associated with regeneration [ 43 , 44 ].…”

“…The ACE is an enzyme and vasoconstrictor playing a crucial role in the renin–angiotensin system by doing conversion of angiotensin I to angiotensin II. As a reminder, it is well documented that angiotensin II is involved in regulation of glucose and insulin levels, and among other effects that induce oxidative stress, inflammation and vascular changes [ 4 , 44 ]. The ACE gene insertion/deletion (I/D) polymorphism is widely studied because this variant has a regulatory role on gene expression and itself is responsible for about 46% of enzyme serum variance [ 1 ].…”

“…APOE is a cholesterol transporter and LDL receptor ligand involved in lipid metabolism, nerve repair and regeneration. Well-known allelic variants e2, e3 and e4 in APOE gene are defined by two functional single nucleotide polymorphisms (SNPs), rs429358 C/T and rs7412 T/C, which cause amino acid changes 112Cys/Arg and 158Arg/Cys, respectively, at the protein level [ 1 , 2 , 44 ]. APOE gene variants have an impact on protein function trough the isoforms E2, E3 and E4, which differ in charge and stability.…”

“…VEGF is chemokine that modulates vascular permeability, regulates angiogenesis and contributes positively to neurogenesis [ 1 , 2 , 44 ]. Related to VEGF gene there are two polymorphic sites, rs6921438 and rs10738760, which contribute to about 50% of VEGF level variation.…”