HSPA5 promoter polymorphisms and risk of Parkinson's disease in Taiwan.
Endoplasmic reticulum (ER) stress induced by misfolded proteins has been implicated in Parkinson's disease (PD) pathogenesis. A malfunction of unfolded protein response (UPR) to ER stress can result in PD as well as other neurodegenerative diseases. Heat shock 70 kDa protein 5 (HSPA5) is one of the UPR chaperones reactive to ER stress to block the apoptotic process. HSPA5 promoter polymorphisms -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) and their derived haplotypes may affect promoter activity of the gene. This study examines whether these HSPA5 promoter polymorphisms are associated with the risk of Taiwanese PD and the age of disease onset using a case-control study. Polymorphisms -415 G/A and -180 del/G were completely linked in our population (D'=1.00, Delta(2)=1.00). The genotype or allele frequency distribution of each HSPA5 polymorphism was not significantly different between the controls (n=341) and the PD patients (n=393). Neither the linked -415 G/A and -180 del/G nor -370 C/T polymorphism influences PD onset age. Our data suggest that the HSPA5 -415 G/A, -370 C/T, and -180 del/G polymorphisms are unlikely to play a major role in risk of developing PD in Taiwan.
Chen
Chiung-Mei
CM
Department of Neurology, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Taipei, Taiwan.
Wu
Yih-Ru
YR
Hu
Fen-Ju
FJ
Chen
Yi-Chun
YC
Chuang
Tzu-Jung
TJ
Cheng
Ya-Fen
YF
Lee-Chen
Guey-Jen
GJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D013624:Taiwan
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones