Analysis of genetic variants related to oxidative stress in patients with Alzheimer’s disease

Abstract Background Alzheimer’s disease (AD) is one of the common neurodegenerative diseases with an incompletely understood pathomechanism. In AD, generation of oxidative stress is observed as a result of dysfunction of the mitochondrial respiratory chain. The effect of this disturbance is the production of reactive oxygen species (ROS). The SOD2 gene is involved in the elimination of ROS. Glutathione S‐transferases (GST) are a group of enzymes with antioxidant properties that protect cells from ROS damage. GSTP1 gene variants may impair the activity of these enzymes. APOE gene, is also related to the regulation of oxidative stress. In AD patients with APOE E4, higher levels of lipid peroxidation are found. The precise nature of the association between oxidative stress and hallmarks of AD pathology is unknown. The aim of the study was to analyze of genetic variants of SOD2 c.47T>C (exon 2) and GSTP1 c.341C>T (exon 6) genes in AD patients, control subjects related to AD cases (CR), and controls subjects without family history of AD (CU). The APOE E4 allele was included in the studies. Method The studies were conducted on 156 individuals (AD and controls). The APOE genotype was determined by real‐time PCR. The SOD2 and GSTP1 genetic variants were determined by HRM and sequencing. The apoE concentration was determined by the ELISA method. Result Variant CC c.47T>C SOD2 was more frequent in CR, while CT in CU. The TT variant of this gene tended to occur more frequently in patients with AD. In AD, the TT variant was more common in the subject without E4 allele (p<0.05). The CC and CT variants of the c.341C>T GSTP1 gene occurred with equal frequency in AD and CR. The TT variant of this gene was not found in the examined subjects. Regardless of the genetic variant of APOE, SOD2, GSTP1, a significantly higher level of apoE was found in CR. Conclusion Genes involved in the regulation of oxidative stress may play an important role in the pathogenesis of AD.