Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder

Abstract

BackgroundDepressive 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/MethodsUsing 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).ResultsWe 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.ConclusionsThe 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.

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

“…Details of the search results are presented in eFigure 1 in the Supplement. We identified 82 studies fulfilling the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Seven studies had interventions, comprising a total of 15 preintervention-postintervention comparisons.…”

Inflammatory profiles of severe treatment-resistant depression

“…The development of these disruptions to biological processes has been attributed to various causes including genetic vulnerabilities (e.g. Czarny et al, 2016) and the experience of severe and/or ongoing psychosocial stress (Miller et al, 2009), although there are likely interactive predisposing and environmental effects.…”

Possible association between DNA repair gene variants and cannabis dependence in a Turkish cohort: a pilot study

“…It has been reported that XRCC1 rs25487 Gln/Gln and Arg/Gln genotypes were more common in patients with schizophrenia than healthy controls [25,26]. However, Celik et al and Czarny et al showed that XRCC1 rs25487 variant had no significant association with obsessive-compulsive disorder (OCD) and recurrent depressive disorder [27,28]. In the present study, we found that XRCC1 rs25487 variant GG genotype and G allele were lower frequency in patients with cannabis dependence (p < 0.05) ( Table 1).…”