Kwiatkowski Dominik, Czarny Piotr, Toma Monika, Korycinska Anna, Sowinska Katarzyna, Galecki Piotr, Bachurska Agnieszka, Bielecka-Kowalska Anna, Szemraj Janusz, Maes Michael, Sliwinski Tomasz
Department of Molecular Genetics, University of Lodz, Lodz, Poland.
Neuropsychobiology. 2016;73(2):98-107. doi: 10.1159/000444643. Epub 2016 Mar 25.
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.
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.
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>G×c.*50C>T CC/CT, c.444T>G×c.*50C>T GG/CT, c.-468T>G×c.*50C>T GG/CT, c.-441G>Ac.*50C>T×c.*50C>T GG/CT, c.*83A>C× c.*50C>T CT/AC, and c.-7C>T×c.*50C>T CT/GG can substantially positively modulate the risk of AD.
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.
导致阿尔茨海默病（AD）的因素之一是神经细胞中由氧化应激和炎症引起的DNA损伤。有人提出，AD的风险可能与DNA修复效率随年龄增长而降低有关。碱基切除修复（BER）是氧化DNA损伤的主要修复系统之一。该系统效率降低的原因之一可能是编码其蛋白质的基因的单核苷酸多态性（SNP）。
用于基因分型的DNA取自281例患者和150例对照的外周血。在本研究中，我们评估了6个BER基因的8个多态性对AD风险的影响。我们分析了以下SNP：APEX1的c.-468T>G和c.444T>G，LIG3的c.*50C>T和c.*83A>C，OGG1的c.977C>G，NEIL1的c.*283C>G，FEN1的c.-441G>A，以及LIG1的c.-7C>T。
我们发现，LIG1的c.-7C>T A/A和LIG3的c.83A>C A/C变体增加了AD风险，而APEX1的c.444T>G G/T、LIG1的c.-7C>T G/、LIG3的c."83A>C C/C变体降低了AD风险。我们还评估了基因-基因相互作用与AD风险之间的关系。我们发现，某些BER基因变体的组合，如c.977C>G×c.50C>T CC/CT、c.444T>G×c."50C>T GG/CT、c.-468T>G×c.*50C>T GG/CT、c.-441G>A×c.*50C>T GG/CT、c.*83A>C×c.*50C>T CT/AC和c.-7C>T×c.*50C>T CT/GG，可显著正向调节AD风险。
总之，我们发现BER基因的多态性可能对AD风险有显著影响，多态性变体的存在可能是AD的重要标志物。
