Glutathione peroxidase 1 Pro198Leu polymorphism in Brazilian Alzheimer's disease patients: relations to the enzyme activity and to selenium status.
OBJECTIVE
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.
PRONUT (Program of Applied Human Nutrition)-FSP/FCF/FEA, University of São Paulo, São Paulo, Brazil. barbaracardoso@usp.br
Bárbara Rita
BR
Cardoso
Thomas Prates
TP
Ong
Wilson
W
Jacob-Filho
Omar
O
Jaluul
Maria Isabel d'Ávila
MI
Freitas
Cristiane
C
Cominetti
Silvia Maria Franciscato
SM
Cozzolino
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D001938:Brazil; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics*; D012643:Selenium / Q000097:blood*; D000094765:Glutathione Peroxidase GPX1
D017931:DNA Primers; D011392:Proline; D005979:Glutathione Peroxidase; D007930:Leucine; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human