Partner: M. Berk

Deakin University (AU)

Recent publications
1.Kwiatkowski D., Czarny P., Toma M., Jurkowska N., Śliwinska A., Drzewoski J., Bachurska A., Szemraj J., Maes M., Berk M., Su K.P., Gałecki P., Śliwiński T., Associations between DNA Damage, DNA Base Excision Repair Gene Variability and Alzheimer's Disease Risk, DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, ISSN: 1420-8008, DOI: 10.1159/000443953, Vol.41, No.3-4, pp.152-171, 2016
Abstract:

Background: Increased oxidative damage to DNA is one of the pathways involved in Alzheimer's disease (AD). Insufficient base excision repair (BER) is in part responsible for increased oxidative DNA damage. The aim of the present study was to assess the effect of polymorphic variants of BER-involved genes and the peripheral markers of DNA damage and repair in patients with AD. Material and Methods: Comet assays and TaqMan probes were used to assess DNA damage, BER efficiency and polymorphic variants of 12 BER genes in blood samples from 105 AD patients and 130 controls. The DNA repair efficacy (DRE) was calculated according to a specific equation. Results: The levels of endogenous and oxidative DNA damages were higher in AD patients than controls. The polymorphic variants of XRCC1 c.580C>T XRCC1 c.1196A>G and OGG1 c.977C>G are associated with increased DNA damage in AD. Conclusion: Our results show that oxidative stress and disturbances in DRE are particularly responsible for the elevated DNA lesions in AD. The results suggest that oxidative stress and disruption in DNA repair may contribute to increased DNA damage in AD patients and risk of this disease. In addition, disturbances in DRE may be associated with polymorphisms of OGG1 and XRCC1.

Keywords:

DNA damage, DNA base excision repair, Alzheimer's disease risk, Dementia, Oxidative stress

Affiliations:
Kwiatkowski D.-other affiliation
Czarny P.-Medical University of Lodz (PL)
Toma M.-University of Lodz (PL)
Jurkowska N.-University of Lodz (PL)
Śliwinska A.-Medical University of Lodz (PL)
Drzewoski J.-Medical University of Lodz (PL)
Bachurska A.-Medical University of Lodz (PL)
Szemraj J.-Medical University of Lodz (PL)
Maes M.-Deakin University (AU)
Berk M.-Deakin University (AU)
Su K.P.-China Medical University Hospital (TW)
Gałecki P.-Medical University of Lodz (PL)
Śliwiński T.-University of Lodz (PL)
2.Czarny P., Kwiatkowski D., Toma M., Gałecki P., Orzechowska A., Bobińska K., Bielecka-Kowalska A., Szemraj J., Berk M., Anderson G., Śliwiński T., Single-nucleotide polymorphisms of genes involved in repair of oxidative DNA damage and the risk of recurrent depressive disorder, Medical Science Monitor, ISSN: 1643-3750, DOI: 10.12659/MSM.898091, Vol.22, pp.4455-4474, 2016
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/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.

Keywords:

Depression, DNA Repair, Inflammation, Oxidative Stress, Polymorphism, Single Nucleotide

Affiliations:
Czarny P.-Medical University of Lodz (PL)
Kwiatkowski D.-other affiliation
Toma M.-University of Lodz (PL)
Gałecki P.-Medical University of Lodz (PL)
Orzechowska A.-other affiliation
Bobińska K.-other affiliation
Bielecka-Kowalska A.-Non-Public Medical Center “Akoria” (PL)
Szemraj J.-Medical University of Lodz (PL)
Berk M.-Deakin University (AU)
Anderson G.-other affiliation
Śliwiński T.-University of Lodz (PL)