Heat Shock Protein 70 and Tumor Necrosis Factor Alpha in Taiwanese Patients with Dementia

Abstract

This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor α (TNF-α) are associated with the risk of Alzheimer’s disease (AD) and vascular dementia (VaD). Using the criteria of the NINCDS-ADRDA and NINDS-AIREN, 125 AD patients, 57 VaD patients and 109 ethnically matched nondemented controls were enrolled. The HSP70-1 –110 A/C and TNF-α –1031 T/C, –863 C/A and –857 C/T polymorphisms were analyzed by means of genotype or haplotype association methods. None of the four genotypes examined showed a statistically significant difference in genotype distribution between the AD cases and controls. However, the HSP70-1 –110 CC genotype occurred more frequently among AD cases (p = 0.0821; odds ratio: 2.08; 95% confidence interval, CI: 0.92–4.98). The overall genotype distribution among the VaD cases tended to be different at the HSP70-1 –110 and TNF-α –1031 sites (p = 0.0604 and 0.0316, respectively). The HSP70-1 –110 CC genotype was more frequent (p = 0.0459), and the association of the –110 CC genotype with VaD was evident (p = 0.0207; odds ratio: 3.22; 95% CI: 1.20–8.87). The more frequent TNF-α –1031 TC genotype (p = 0.0614) was also evidently associated with VaD (p = 0.0209; odds ratio: 2.32; 95% CI: 1.14–4.78). Multivariate analysis demonstrated the synergistic effect of the HSP70-1 –110 CC and TNF-α –1031 TC/CC genotypes on VaD (p = 0.0091; odds ratio: 10.09; 95% CI: 2.01–75.97). Haplotype analysis among TNF-α –1031, –863, –857 sites revealed that –1031C–857C may act as a risk haplotype among VaD cases (p = 0.0132, odds ratio: 2.26; 95% CI: 1.19–4.33). Our results suggest a potential protective role for HSP70 in both VaD and AD, whereas TNF-α may act as a risk factor only for VaD, and not for AD.