Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder
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2016-11-20
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Medical Science Monitor
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INT SCIENTIFIC INFORMATION, INC
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Psychiatry
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Journal Article
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Czarny, P., Kwiatkowski, D., Toma, M., Gałecki, P., Orzechowska, A., Bobińska, K., Bielecka-Kowalska, A., Szemraj, J., Berk, M., Anderson, G. & Śliwiński, T. (2016). Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder. Medical Science Monitor, 22, pp.4455-4474. https://doi.org/10.12659/MSM.898091.
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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.