Association of NAD(P)H:Quinone Oxidoreductase 1 Polymorphism and Alzheimer’s Disease in Chinese

Abstract

Several lines of evidence support a role of oxidative stress in the pathology of Alzheimer's disease (AD). NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyzes the two-electron reduction of quinones, preventing their participation in redox cycling and subsequent generation of reactive oxygen species. We examined association between the NQO1 C609T gene polymorphism and sporadic AD in a Chinese population comprising 311 AD patients and 330 controls. Our results showed a higher T-allele frequency in the AD cases compared with the controls. The difference was close to but did not reach statistically significant level [p = 0.059; odds ratio (OR) T versus C = 1.236; 95% confidence interval (95% CI), 0.992-1.540]. A significantly low C/C genotype frequency in the AD cases compared with the controls was detected (p = 0.025; OR C/C versus C/T + T/T = 0.674; 95% CI, 1.049-2.098) and APOE epsilon4 status analysis revealed significant difference in the APOE epsilon4 non-carriers (p = 0.036; OR = 0.633; 95% CI, 1.027-2.427). In the > or =65 years samples, significantly low C/C frequency in the AD cases in comparison with the controls was observed in the APOE epsilon4 non-carriers (p = 0.045; OR = 0.595; 95% CI, 1.010-2.794). These results indicated that the C/C genotype had a possible protective effect against AD development, and the T allele might be a weak risk factor for late onset AD.

E3 Ligase STUB1/CHIP Regulates NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Accumulation in Aged Brain, a Process Impaired in Certain Alzheimer Disease Patients

“…In age-associated pathologies such as AD, NQO1 protein level is reported to be high in some histological analysis (36,37). On the other hand, studies on correlating AD with NQO1 C609T polymorphism proved inconclusive (13,55). Furthermore, genetic screening did not find NQO1 gene expression to be associated with the onset of AD (56).…”

“…People carrying the polymorphic C609T NQO1 gene show increased sensitivity to benzene toxicity (9), are at an increased risk for development of different solid tumors and leukemia (10 -12), and are also suggested to be more susceptible to neurodegenerative diseases such as Alzheimer disease (AD) (13). To date, NQO1 protein accumulation has been shown to be regulated mainly at the transcriptional level by Nrf1 and Nrf2 (14), and not much is known on the regulation of NQO1 at the posttranslational level.…”

The Parkinson’s-associated protein DJ-1 regulates the 20S proteasome

“…refs 2,33), and both are associated with neurodegenerative diseases. In particular, mutations in NQO1 lead to an increased risk of developing Alzheimer's disease 34,35 , while mutations in DJ-1 are linked to familial PD (reviewed in refs 1,2).…”

Genetics of primary progressive multiple sclerosis

“…This functional allele affects individual vulnerability to oxidative damage (Dinkova-Kostova and Talalay, 2000;Ross et al, 2000) and as such may influence MS risk. This allele is implicated in other degenerative diseases, including Alzheimer's disease (Bian et al, 2008) and Parkinson's disease (Shao et al, 2001). Whether this allele also correlates with MS disability is not known.…”