ABSTRACT
There is considerable evidence that oxidative DNA damage is increased, DNA repair capacity is decreased in patients with Alzheimer's disease. Base excision repair is the major pathway in removal of oxidative DNA damage. 8-oxo-deoxyguanosine DNA glycosylase 1 (OGG1) is the enzyme which is involved in the first step of this repair process. Alterations in DNA repair capacity may be related with polymorphisms in DNA repair genes. In order to investigate the effect of OGG1 Ser326Cys polymorphism on oxidative DNA damage level, OGG1 genotyping was performed, basal and oxidative DNA damage in lymphocytes and 8-OHdG level in plasma were examined in patients with Alzheimer's disease. Basal and oxidative DNA damage and 8-OHdG level were measured by OGG1-modified comet assay and enzyme-linked immunoassay, respectively. OGG1 genotyping was performed by polymerase chain reaction- restriction fragment length polymorphism assay. Basal and oxidative DNA damage and plasma 8-OHdG levels were found to be higher in the Alzheimer's disease group than those in the control group (Pâ¯<â¯0.001). In the Alzheimer's disease group, the levels of oxidative DNA damage was higher in the patients having OGG1 (Ser326Cysâ¯+â¯Cys326Cys) genotype than those in the patients having OGG1 Ser326Ser genotype. It was concluded that oxidative DNA damage is increased in patients with Alzheimer's disease and OGG1 Ser326Cys polymorphism may be responsible for this increase.
Subject(s)
Alzheimer Disease/genetics , DNA Damage/physiology , DNA Glycosylases/genetics , DNA Repair/physiology , Oxidative Stress/physiology , Polymorphism, Single Nucleotide/physiology , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/metabolism , Case-Control Studies , DNA Glycosylases/metabolism , Female , Humans , Male , Middle AgedABSTRACT
The aim of the current study was to compare oxidative DNA damage, DNA susceptibility to oxidation, and ratio of GSH/GSSG in patients with Alzheimer's disease (AD) treated with acetylcholinesterase inhibitor (AChEI) and combined AChEI+memantine. The study included 67 patients with AD and 42 volunteers as control. DNA damage parameters (strand breaks, oxidized purines, H2O2-induced DNA damage) in lymphocyte DNA and GSH/GSSG ratio in erythrocytes were determined by the comet assay and spectrophotometric assay, respectively. DNA damage was found to be higher, GSH/GSSG ratio was found to be lower in the AD group than those in the control group. DNA strand breaks and H2O2-induced DNA damage were lower in the patients taking AChEI+memantine than those in the patients taking AChEI but no significant difference was determined between the groups for oxidized purines and GSH/GSSG ratio. In conclusion, increased systemic oxidative DNA damage and DNA susceptibility to oxidation may be resulted from diminished GSH/GSSG ratio in AD patients. Although DNA strand breaks and H2O2-induced DNA damage are lower in the AD patients treated with combined AChEI and memantine, this may not indicate protective effect of memantine against DNA oxidation due to similar levels of oxidized purines in the patients treated with AChEI and AChEI+memantine.
