Heat shock protein 70 and tumor necrosis factor alpha in Taiwanese patients with dementia.
This study was to determine whether polymorphisms of heat shock protein 70-1 (HSP70-1) and tumor necrosis factor alpha (TNF-alpha) 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-alpha -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-alpha -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-alpha -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-alpha -1031 TC/CC genotypes on VaD (p=0.0091; odds ratio: 10.09; 95% CI: 2.01-75.97). Haplotype analysis among TNF-alpha -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-alpha may act as a risk factor only for VaD, and not for AD.
Fung
H C
HC
Second Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan.
Chen
C M
CM
Wu
Y R
YR
Hsu
W C
WC
Ro
L S
LS
Lin
J C
JC
Chang
K H
KH
Wang
H K
HK
Lin
S J
SJ
Chan
H
H
Lin
Y Y
YY
Wei
S L
SL
Hsu
Y
Y
Hwang
J C
JC
Tung
L C
LC
Lee-Chen
G-J
GJ
D000368:Aged; D000483:Alleles; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D003704:Dementia / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D013624:Taiwan; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; C081884:heat-shock protein 70.1