Analysis of heat-shock protein 70 gene polymorphisms and the risk of Parkinson's disease.
Parkinson's disease (PD) involves several genetic and environmental components. Heat-shock protein 70, a chaperone that is up-regulated in stress responses and that refolds protein, may be involved in the pathogenesis of PD. We have investigated the association of polymorphisms -110 A/C, +190 G/C, +1267 A/G, +2074 G/C, and +2437 G/C in the 5' and coding regions of the HSP70-1, HSP70-2, and HSP70-hom genes with the risk of PD by screening DNA samples from 274 PD patients and 183 controls in assays based on the polymerase chain reaction. There was no statistically significant difference in genotype distribution between patients and controls for the three coding-region polymorphisms in HSP70-2 and HSP70-hom. However, for HSP70-1, the overall genotype distribution was significantly different at the -110 site (P=0.004) and tended to be different at the +190 site (P=0.012) between patients and controls. The frequencies of the -110 CC and +190 CC genotypes were significantly higher in PD patients than in controls (P=0.001 and 0.006, respectively). Both -110 CC (odds ratio: 2.91; 95% CI: 1.51-5.96; P=0.002) and +190 CC (odds ratio: 3.59; 95% CI: 1.53-9.88; P=0.006) genotypes were significantly associated with PD. Reporter constructs containing the -110 A allele cloned into a luciferase reporter plasmid drove marginally higher transcriptional activity of HSP70-1 compared with the -110 C allele in both control and heat-shocked IMR32 and 293 cells. Therefore, -110 A/C may be a functional polymorphism in the 5' promoter region of HSP70-1 and may affect susceptibility to PD.
Wu
Yih-Ru
YR
Second Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taipei, Taiwan.
Wang
Cheng-Kuang
CK
Chen
Chiung-Mei
CM
Hsu
Yuying
Y
Lin
Sih-Jing
SJ
Lin
Yi-Ying
YY
Fung
Hon-Chung
HC
Chang
Kuo-Hsuan
KH
Lee-Chen
Guey-Jen
GJ
D024506:5' Flanking Region; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002460:Cell Line; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D018840:HSP70 Heat-Shock Proteins