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.

Association Between Open-Angle Glaucoma and Gene Polymorphism for Heat-Shock Protein 70-1

“…23,27 However, in contrast to our results, the frequency of the CC genotype is signifi cantly increased among patients with these diseases. The disparity between results might refl ect differences between ethnic groups and diseases.…”

“…Allele frequency of the A−110C polymorphism in this study is compatible with that reported previously in Japanese, 28 although it is substantially different from the allele frequencies in reports from Taiwan. 23,27 Fung et al 27 reported that the frequency of the −110CC genotype is increased among patients with Alzheimer's disease or vascular dementia, and suggested that lower HSP70 expression may be associated with the development of these diseases. As mentioned above, HSPs and the consequent immune response to these proteins may have protective or pathogenic effects.…”

Genetics of Late‐Onset Alzheimer′s Disease: Update from the Alzgene Database and Analysis of Shared Pathways

“…The gene-encoding TNF (chromosome 6) has been extensively investigated as a susceptibility AD gene. One SNP (rs4647198) was significantly associated with LOAD in Asian populations [125–127] ( N minor = 301; OR 1.37 95% CI: 1.05–1.08). Increase in the serum levels of TNF-alpha following acute inflammatory events was found to correlate with a 2-fold increase in the rate of cognitive decline over a 6-month period in AD patients.…”

Genetics of vascular dementia – review from the ICVD working group

“…Two polymorphisms (Q192R and L55M) of PON1 were associated with a higher risk of VaD in Indian and French populations [26–28], but these findings for Q192R were not confirmed in two other studies on European populations [29, 30]. Several genes related to inflammation have also been related to VaD, including two polymorphisms in the TNF-α in Europeans [31] and Asians [32]. In addition, an association between VaD and TGF-β1 was described in two Asian reports [33, 34].…”