Association between Single-Nucleotide Polymorphisms of the hOGG1, NEIL1, APEX1, FEN1, LIG1, and LIG3 Genes and Alzheimer's Disease Risk

Background: One of the factors that contribute to Alzheimer's disease (AD) is the DNA damage caused by oxidative stress and inflammation that occurs in nerve cells. It has been suggested that the risk of AD may be associated with an age dependent reduction of the DNA repair efficiency. Base excision repair (BER) is, among other things, a main repair system of oxidative DNA damage. One of the reasons for the reduced efficiency of this system may be single-nucleotide polymorphisms (SNP) of the genes encoding its proteins. Methods: DNA for genotyping was obtained from the peripheral blood of 281 patients and 150 controls. In the present study, we evaluated the impact of 8 polymorphisms of 6 BER genes on the AD risk. We analyzed the following SNP: c.-468T>G and c.444T>G of APEX1, c.*50C>T and c.*83A>C of LIG3, c.977C>G of OGG1, c.*283C>G of NEIL1, c.-441G>A of FEN1, and c.-7C>T of LIG1. Results: We showed that the LIG1 c.-7C>T A/A and LIG3 c.*83A>C A/C variants increased, while the APEX1 c.444T>G G/T, LIG1 c.-7C>T G/, LIG3 c.*83A>C C/C variants reduced, the AD risk. We also evaluated the relation between gene-gene interactions and the AD risk. We showed that combinations of certain BER gene variants such as c.977C>Gxc.*50C>T CC/CT, c./111T>Gxc.*50C>T GG/CT, c.-468T>Gxc.*50C>T GG/CT, c.-441G>Ac.*50C>Txc.*50C>T GG/CT, c.*83A>Cx c.*50C>T CT/AC, and c.-7C>Txc.*50C>T CT/GG can substantially positively modulate the risk of AD. Conclusions: In conclusion, we revealed that polymorphisms of BER genes may have a significant effect on the AD risk, and the presence of polymorphic variants may be an important marker for AD. (C) 2016 S. Karger AG, Basel