Oncotarget

Research Papers:

Biothiols and oxidative stress markers and polymorphisms of TOMM40 and APOC1 genes in Alzheimer's disease patients

Michal Prendecki, Jolanta Florczak-Wyspianska, Marta Kowalska, Jan Ilkowski, Teresa Grzelak, Katarzyna Bialas, Malgorzata Wiszniewska, Wojciech Kozubski and Jolanta Dorszewska _

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Oncotarget. 2018; 9:35207-35225. https://doi.org/10.18632/oncotarget.26184

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Abstract

Michal Prendecki1, Jolanta Florczak-Wyspianska2, Marta Kowalska1, Jan Ilkowski3, Teresa Grzelak4, Katarzyna Bialas1, Malgorzata Wiszniewska5,6, Wojciech Kozubski2 and Jolanta Dorszewska1

1Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland

2Chair and Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland

3Department of Emergency Medicine, Poznan University of Medical Sciences, Poznan, Poland

4Division of Biology of Civilization-Linked Diseases, Department of Chemistry and Clinical Biochemistry, Poznan University of Medical Sciences, Poznan, Poland

5Faculty of Health Care, Stanislaw Staszic University of Applied Sciences in Pila, Pila, Poland

6Department of Neurology, Specialistic Hospital in Pila, Pila, Poland

Correspondence to:

Jolanta Dorszewska, email: dorszewskaj@yahoo.com

Keywords: biothiols; oxidative stress; gene polymorphism; Alzheimer’s disease

Received: June 27, 2018    Accepted: September 01, 2018    Published: October 16, 2018

ABSTRACT

Alzheimer’s disease (AD) is a progressive disease, with frequently observed improper biothiols turnover, homocysteine (Hcy) and glutathione (GSH). GSH protects cells from oxidative stress and may be determined by 8-oxo-2’-deoxyguanosine (8-oxo2dG) level and its repair enzyme 8-oxoguanine DNA glycosylase (OGG1). The presence of unfavorable alleles, e.g., in APOE cluster, TOMM40 or APOC1 is known to facilitate the dementia onset under oxidative stress.

The aim of the study was to analyze rs1052452, rs2075650 TOMM40 polymorphisms, rs4420638 APOC1, and their correlation with Hcy, GSH, 8-oxo2dG, OGG1 levels in plasma of AD patients and controls.

We recruited 230 individuals: 88 AD, 80 controls without (UC), 62 controls with (RC) positive family history of AD. The TOMM40 genotype was determined by HRM and capillary electrophoresis, while APOC1 by HRM. The concentrations of OGG1, 8-oxo2dG were determined by ELISA, whereas Hcy, GSH by HPLC/EC.

We showed that over 60% of AD patients had increased Hcy levels (p<0.01 vs. UC, p<0.001 vs. RC), while GSH (p<0.01 vs. UC), 8-oxo2dG (p<0.01 vs. UC, p<0.001 vs. RC) were reduced. Minor variants: rs10524523-L, rs4420638-G, rs2075650-G were significantly overrepresented in AD. For rs4420638-G, rs2075650-G variants, the association remained significant in APOE E4 non-carriers. The misbalance of analyzed biothiols, and 8-oxo2dG, OGG1 were more pronounced in carriers of major variants: rs10524523-S/VL, rs4420638-A, rs2075650-A.

We showed, for the first time, that APOC1 and TOMM40 rs2075650 polymorphisms may be independent risk factors of developing AD, whose major variants are accompanied by disruption of biothiols metabolism and inefficient removal of DNA oxidation.


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