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巴西阿尔茨海默病患者谷胱甘肽过氧化物酶1 Pro198Leu多态性:与酶活性及硒状态的关系

Glutathione peroxidase 1 Pro198Leu polymorphism in Brazilian Alzheimer's disease patients: relations to the enzyme activity and to selenium status.

作者信息

Cardoso Bárbara Rita, Ong Thomas Prates, Jacob-Filho Wilson, Jaluul Omar, Freitas Maria Isabel d'Ávila, Cominetti Cristiane, Cozzolino Silvia Maria Franciscato

机构信息

PRONUT (Program of Applied Human Nutrition)-FSP/FCF/FEA, University of São Paulo, São Paulo, Brazil.

出版信息

J Nutrigenet Nutrigenomics. 2012;5(2):72-80. doi: 10.1159/000338682. Epub 2012 Jun 7.

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.

摘要

背景/目的:氧化应激在阿尔茨海默病(AD)中起核心作用。胞质谷胱甘肽过氧化物酶(GPx1)的Pro198Leu多态性似乎与该酶活性降低有关,但尚无针对AD患者的研究。因此,本研究旨在确定AD患者中GPx1 Pro198Leu多态性的频率,并验证其与谷胱甘肽过氧化物酶(GPx)活性及硒(Se)状态的关系。

方法

本研究纳入一组AD老年患者(n = 28),并与对照组(n = 29)进行比较。通过氢化物发生原子吸收光谱法测定血硒浓度。使用商用试剂盒测定GPx活性,采用扩增DNA测序法检测多态性。

结果

两组间基因型分布无差异。变异等位基因频率在AD组为0.179,在对照组为0.207。尽管不同基因型个体的GPx活性无差异,但与Pro/Pro基因型的对照受试者相比,Pro/Pro基因型的AD患者血硒水平较低,而Pro/Leu组未发现此差异。此外,红细胞硒浓度与GPx活性之间的关联受Pro198Leu基因型影响。

结论

结果表明,这种多态性明显影响了AD患者的硒状态,该领域需要更多研究。

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