title: Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA Damage and the Risk of Recurrent Depressive Disorder.
abstract: BACKGROUND 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.
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czarny
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kwiatkowski
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Toma
authors.affiliation: Department of Adult Psychiatry, Medical University of Łódź, Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gałecki
authors.affiliation: Department of Adult Psychiatry, Medical University of Łódź, Łódź, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Orzechowska
authors.affiliation: Department of Adult Psychiatry, Medical University of Łódź, Łódź, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Bobińska
authors.affiliation: , Non-Public Medical Center "Akoria", Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielecka-Kowalska
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Łódź, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: IMPACT Research Center, Deakin University, Geelong, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Clinical Research Communications Centre, CRC Scotland & London, London, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.affiliation: Department of Molecular Genetics, University of Łódź, Łódź, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Śliwiński
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D000072481:DNA Ligase ATP / Q000235:genetics / Q000378:metabolism; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000235:genetics / Q000378:metabolism; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
chemical_list: D004268:DNA-Binding Proteins; C000607892:LIG1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; D004247:DNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D045585:Flap Endonucleases; C468317:FEN1 protein, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human