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Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder

Czarny, Piotr, Kwiatkowski, Dominik, Toma, Monika, Gałecki, Piotr, Orzechowska, Agata, Bobińska, Kinga, Bielecka-Kowalska, Anna, Szemraj, Janusz, Berk, Michael, Anderson, Greg and Śliwiński, Tomasz 2016, Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder, Medical science monitor, vol. 22, pp. 4455-4474, doi: 10.12659/MSM.898091.

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Title Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder
Author(s) Czarny, Piotr
Kwiatkowski, Dominik
Toma, Monika
Gałecki, Piotr
Orzechowska, Agata
Bobińska, Kinga
Bielecka-Kowalska, Anna
Szemraj, Janusz
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Anderson, Greg
Śliwiński, Tomasz
Journal name Medical science monitor
Volume number 22
Start page 4455
End page 4474
Total pages 20
Publisher International Scientific Literature
Place of publication Smithtown, N.Y.
Publication date 2016-11-20
ISSN 1234-1010
1643-3750
Keyword(s) depression
DNA repair
inflammation
oxidative stress
polymorphism, single nucleotide
Summary 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.
Language eng
DOI 10.12659/MSM.898091
Field of Research 170101 Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Socio Economic Objective 920410 Mental Health
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Medical Science Monitor
Free to Read? Yes
Use Rights Creative Commons Attribution Non-Commercial No-Derivatives licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30091012

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.