Impact of Single Nucleotide Polymorphisms of Base Excision Repair Genes on DNA Damage and Efficiency of DNA Repair in Recurrent Depression Disorder

Piotr Czarny,Janusz Szemraj,Monika Talarowska,Piotr Galecki,Michael Maes,Joanna Kubiak,Tomasz Sliwinski,Monika Toma,Dominik Kwiatkowski,Agnieszka Sliwinska

doi:10.1007/s12035-016-9971-6

Piotr Czarny, Janusz Szemraj + Show 8 more

Open Access

https://doi.org/10.1007/s12035-016-9971-6

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Abstract

Elevated level of DNA damage was observed in patients with depression. Furthermore, single nucleotide polymorphisms (SNPs) of base excision repair (BER) genes may modulate the risk of this disease. Therefore, the aim of this study was to delineate the association between DNA damage, DNA repair, the presence of polymorphic variants of BER genes, and occurrence of depression. The study was conducted on peripheral blood mononuclear cells of 43 patients diagnosed with depression and 59 controls without mental disorders. Comet assay was used to assess endogenous (oxidative) DNA damage and efficiency of DNA damage repair (DRE). TaqMan probes were employed to genotype 12 SNPs of BER genes. Endogenous DNA damage was higher in the patients than in the controls, but none of the SNPs affected its levels. DRE was significantly higher in the controls and was modulated by BER SNPs, particularly by c.977C>G–hOGG1, c.972G>C–MUTYH, c.2285T>C–PARP1, c.580C>T–XRCC1, c.1196A>G–XRCC1, c.444T>G–APEX1, c.-468T>G–APEX1, or c.*50C>T–LIG3. Our study suggests that both oxidative stress and disorders in DNA damage repair mechanisms contribute to elevated levels of DNA lesions observed in depression. Lower DRE can be partly attributed to the presence of specific SNP variants.

Highlights

Even though depression disorder is common, its pathogenesis still remains elusive
Our study suggests that both oxidative stress and disorders in DNA damage repair mechanisms contribute to elevated levels of DNA lesions observed in depression
NLRP3 is involved in DNA damage response (DDR) since its knockout increases the effectiveness of double-strand break repair and base excision repair (BER) [7]

Summary

Introduction

Even though depression disorder (including the recurrent type—rDD) is common, its pathogenesis still remains elusive. The activated immune-inflammatory pathways present in depression often coexist with increased oxidative stress, as indicated by elevated levels of lipid peroxidation and production of reactive oxygen species (ROS) in patients affected by the disease [6, 8]. DNA is one of the consequences of oxidative stress in depression and is indicated by increased 8-oxoguanine (8-oxoG) in the urine, serum, and peripheral blood mononuclear cells (PBMCs) of depressed patients [9,10,11,12,13,14]. We have genotyped 12 SNPs located in either coding or regulatory regions of BER genes and estimated the level of endogenous DNA damage as well as the efficiency of DNA damage repair (DRE) in PBMCs of patients with diagnosed rDD and healthy controls. Its purity was controlled by acquiring the absorbance ratio at 260 and 280 nm

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