Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Piotr Gałecki, Agata Orzechowska, Kinga Bobińska, Anna Bielecka-Kowalska, Janusz Szemraj, Michael Berk, George Anderson, Tomasz Śliwiński
(Department of Molecular Genetics, University of Łódź, Łódź, Poland)
Med Sci Monit 2016; 22:4455-4474
Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins.
MATERIAL AND METHODS: Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538) of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.-7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of APEX1 in 599 samples (288 rDD patients and 311 controls).
RESULTS: We found a strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt correction. Polymorphisms of LIG3 were also associated with early onset versus late onset depression, whereas the c.-468T>G polymorphism showed the opposite association.
CONCLUSIONS: The SNPs of genes involved in the repair of oxidative DNA damage may modulate rDD risk. Since this is an exploratory study, the results should to be treated with caution and further work needs to be done to elucidate the exact involvement of DNA damage and repair mechanisms in the development of this disease.
Keywords: DNA - metabolism, Case-Control Studies, Aged, Adult, DNA Damage, DNA Ligase ATP - metabolism, DNA Ligases - metabolism, DNA Repair, DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism, DNA-Binding Proteins - metabolism, Depression - metabolism, Depressive Disorder - metabolism, Female, Flap Endonucleases - metabolism, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Middle Aged, Oxidative Stress - genetics, Poly (ADP-Ribose) Polymerase-1 - metabolism, Polymorphism, Single Nucleotide