Effects of APOE rs429358, rs7412 and GSTM1/GSTT1 Polymorphism on Plasma and Erythrocyte Antioxidant Parameters and Cognition in Old Chinese Adults

Linhong Yuan,Rong Xiao,Bo Wang,Can Cai,Li Dong,Jinmeng Liu,Sisi Wang

doi:10.3390/nu7105391

Abstract

Apolipoprotein E (APOE) and oxidative damage were correlated with the risk of Alzheimer’s disease (AD). Glutathione S-transferase (GST) polymorphism was proved to be associated with body antioxidant capacity and involved in the oxidative damage related chronic diseases. To explore the combined effects of APOE rs429358, rs7412 and GSTM1/T1 polymorphism on antioxidant parameters and cognition in old Chinese adults, a community-based cross-sectional study was carried out in 477 Chinese adults aged from 55 to 75. Information on demography and lifestyle of the participants was collected with a questionnaire. Cognitive function was measured by using a Montreal Cognitive Assessment (MoCA) test. Fasting venous blood samples were collected for APOE rs429358, rs7412 and GSTM1/T1 genotyping, and parameter measurement. No association of APOE rs7412, rs429358 and GSTM1/T1 polymorphisms with cognition was detected in the old Chinese adults. APOE rs429358, rs7412 polymorphism was mainly associated with plasma α-tocopherol, low density lipoprotein cholesterol (LDL-C) and plasma total antioxidant capacity (T-AOC) levels (p < 0.05). Interaction of APOE rs429358 and GSTT1 genotype on the plasma triglyceride (TG) level and erythrocyte catalase (CAT) and GST enzyme activities were detected (p < 0.05). The subjects with APOE rs429358 T/C + C/C and GSTT1− genotype were found to have the highest plasma TG level, erythrocyte CAT enzyme activity, and the lowest GST enzyme activity compared to subjects with other genotypes (p < 0.05). Lowest erythrocyte CAT enzyme activity and highest glutathione peroxidase (GSH-Px) enzyme activity were detected in the subjects with APOE rs7412 T/C + T/T and GSTM1+ genotype as compared with subjects with other genotypes. The levels of plasma and erythrocyte antioxidant parameters were APOE genotype associated. GSTM1 or GSTT1 genotype modified the influence of APOE rs7412, rs429358 polymorphism on antioxidant parameters.

Highlights

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder leading to dementia
Due to the much lower frequencies of Apolipoprotein E (APOE) ε4 alleles in Asian populations compared to that in the Northern European population, in the present study, we evaluated the influence of APOE rs429358, rs7412 polymorphisms, respectively, on plasma, erythrocyte antioxidant parameters and cognition in old Chinese adults
Among the 477 subjects, only three subjects were of the APOE rs429358 C/C genotype; only three subjects were of the APOE rs7412 T/T genotype

Summary

Introduction

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder leading to dementia. Post-mortem and in vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment [5,6,7]. This situation is combined with a reduction of most enzymatic antioxidants defenses, like glutathione peroxidase (GPX), glutathione S-transferase (GST) and superoxide dismutase (SOD) [8] accompanied with elevated markers of lipid peroxidation, like malondialdehyde (MDA) [9,10]. Oxidative damage might represent a potential therapeutic target for slowing the onset and progression of AD [11]

Methods

Results

Conclusion