| 1. | Sliwinska A.♦, Sitarek P.♦, Toma M.♦, Czarny P.♦, Synowiec E.♦, Krupa R.♦, Wigner P.♦, Bialek K.♦, Kwiatkowski D.♦, Korycinska A.♦, Majsterek I.♦, Szemraj J.♦, Galecki P.♦, Sliwinski T.♦, Decreased expression level of BER genes in Alzheimer's disease patients is not derivative of their DNA methylation status, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, ISSN: 0278-5846, DOI: 10.1016/j.pnpbp.2017.07.010, Vol.79, pp.311-316, 2017 Abstract:Background: Neurodegeneration in Alzheimer's disease can be caused by accumulation of oxidative DNA damage resulting from altered expression of genes involved in the base excision repair system (BER). Promoter methylation can affect the profile of BER genes expression. Decreased expression of BER genes was observed in the brains of AD patients.
Aim of the study: The aim of our study was to compare the expression and methylation profiles of six genes coding for proteins involved in BER, namely: hOGG1, APE1, MUTYH, NEIL1, PARP1 and XRCC1, in the peripheral blood cells of AD patients and healthy volunteers.
Methods: The study consisted of 100 persons diagnosed with Alzheimer's disease according to DSM-IV criteria, and 110 healthy volunteers. DNA and total RNA were isolated from venous blood cells. Promoter methylation profiles were obtained by High Resolution Melting (HRM) analysis of bisulfide converted DNA samples. Real-time PCR with TaqMan probes was employed for gene expression analysis.
Results: APE1, hOGG1, MUTYH, PARP1 and NEIL1 were significantly (p < 0.001) down-regulated in the lymphocytes of AD patients, as compared to healthy volunteers. Expression of XRCC1 didn't differ significantly between both groups. We did not find any differences in the methylation pattern of any of the investigated BER genes.
Conclusions: The methylation status of promoters is not associated with downregulation of BER genes. Our results show that downregulation of BER genes detected in peripheral blood samples could reflect the changes occurring in the brain of patients with AD, and may be a useful biomarker of this disease. Keywords:Alzheimer's disease, DNA base excision repair genes, Gene expression, Promoter methylation Affiliations:| Sliwinska A. | - | Medical University of Lodz (PL) | | Sitarek P. | - | Medical University of Lodz (PL) | | Toma M. | - | University of Lodz (PL) | | Czarny P. | - | Medical University of Lodz (PL) | | Synowiec E. | - | University of Lodz (PL) | | Krupa R. | - | University of Lodz (PL) | | Wigner P. | - | University of Lodz (PL) | | Bialek K. | - | University of Lodz (PL) | | Kwiatkowski D. | - | other affiliation | | Korycinska A. | - | University of Lodz (PL) | | Majsterek I. | - | Medical University of Lodz (PL) | | Szemraj J. | - | Medical University of Lodz (PL) | | Galecki P. | - | Medical University of Lodz (PL) | | Sliwinski T. | - | University of Lodz (PL) |
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