Glutathione Peroxidase 1 Pro198Leu Polymorphism in Brazilian Alzheimer’s Disease Patients: Relations to the Enzyme Activity and to Selenium Status

Abstract

Background/Aims: Oxidative stress plays a central role in Alzheimer’s disease (AD). Pro198Leu cytosolic glutathione peroxidase (GPx1) polymorphism seems to be associated with a lower activity of this enzyme, but there are no studies with AD patients. Thus, the aim was to determine the frequency of the GPx1 Pro198Leu polymorphism in AD patients and to verify its relation to glutathione peroxidase (GPx) activity and selenium (Se) status. Methods: The study was carried out in a group of AD elderly (n = 28) compared to a control group (n = 29). Blood Se concentrations were measured through hydride generation atomic absorption spectroscopy. GPx activity was determined using a commercial kit, and the polymorphism using amplified DNA sequencing. Results: The distribution of genotypes was not different between groups. The variant allele frequency was 0.179 (AD group) and 0.207 (control group). Although no differences regarding GPx activity were found between individuals with different genotypes, lower blood Se levels were found in Pro/Pro AD patients compared to Pro/Pro control subjects, which was not found in the Pro/Leu groups. Moreover, the association between the erythrocyte Se concentration and GPx activity was affected by the Pro198Leu genotype. Conclusions: Results indicate that this polymorphism had apparently affected Se status in AD patients and that more studies in this field are necessary.

rs2070424 of the SOD1 gene is associated with risk of Alzheimer's disease

“…Meta-analysis including data of Wiener et al and ours could not be conducted due to lack of raw data in Wiener's publication. Similarly to Cardoso et al [7] we did not find any association between rs1050450 of the GPx-1 gene and AD risk.…”

“…There are only few studies evaluating the importance of ADS gene single nucleotide polymorphisms (SNPs) as risk factors of AD. So far, there were two studies evaluating the significance of one SNP of the catalase gene (rs1001179) [4,5], one -the significance of four SNPs of the SOD2 gene (rs2758346, r4880, rs2855116 and rs5746136) [6] and another one evaluating the significance of the rs1050450 SNP of the GPx-1 gene [7]. Only the study on the SOD2 gene, yielded positive results.…”

Association between GPx-1 Polymorphisms and Personality Traits in Healthy Chinese-Han Subjects

“…A study of the Ecuadorian population (Paz-y-Mino et al 2010) showed that the Gx1-Leu allele increased the risk of AD. Interestingly, Cardoso et al did not observe a difference in the genotypic frequency between AD patients and the control groups in a Brazilian population (Cardoso et al 2012). However, a case-controlled study on the association of GPx-1 and…”

“…There is considerable evidence that GPx has a strong association with some diseases, many with links to the DA system (Bai et al 2017;Cardoso et al 2012;Gardaneh et al 2011;Paz-y-Mino et al 2010;Power and Blumbergs 2009). In fact, DA is a major source of ROS in the central nervous system, as it can produce ROS and DA-quinone during its autooxidation (Zucca et al 2014).…”

Status de selênio de uma população residente em área de risco de contaminação por mercúrio. Influência de polimorfismos e ação sobre o estresse oxidativo

“…Cardoso et al (2012), ao determinar o polimorfismo em um grupo de 28 idosos com doença de Alzheimer, observaram que 75% apresentaram genótipo Pro/Pro, 14% de heterozigotos e 11% de Leu/Leu. No mesmo estudo, no grupo controle, formado por 29 idosos sem a doença, os pesquisadores encontraram 72% com genótipo Pro/Pro, 14% de Pro/Leu e 14% de homozigotos Leu/Leu.…”