Impact of Single Nucleotide Polymorphisms of Base Excision Repair Genes on DNA Damage and Efficiency of DNA Repair in Recurrent Depression Disorder.
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.
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.|Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
Piotr
P
Czarny
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.
Dominik
D
Kwiatkowski
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.
Monika
M
Toma
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.
Joanna
J
Kubiak
Department of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland.
Agnieszka
A
Sliwinska
Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland.
Monika
M
Talarowska
Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
Janusz
J
Szemraj
IMPACT Strategic Research Centre, Barwon Health, Deakin University School of Medicine, Geelong, Victoria, Australia.|Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand.|Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil.
Michael
M
Maes
Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland.
Piotr
P
Galecki
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland. tomsliw@biol.uni.lodz.pl.
Tomasz
T
Sliwinski
D000483:Alleles; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
Base excision repair; DNA damage; DNA repair; Oxidative stress; Recurrent depression disorder; Single nucleotide polymorphism