title: alpha-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson's disease.
abstract: Increased alpha-synuclein expression may be involved in the pathogenesis of Parkinson's disease (PD). We investigated the association of Rep1 microsatellite and RsaI T-to-C substitution in the alpha-synuclein promoter region with the risk of PD by a case-control study. The RsaI C/C genotype and C allele were found less frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C haplotype (OR = 0.57, 95% CI = 0.36-0.90) with PD was evident. The quantitative real-time PCR study showed that the alpha-synuclein mRNA expression was increased (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0-T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs containing the RsaI C allele drove significantly lower transcriptional activity compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest that the RsaI T-to-C substitution may have a functional relevance to the susceptibility to PD.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: C K
authors.initials: CK
authors.lastname: Wang
authors.forename: C M
authors.initials: CM
authors.lastname: Chen
authors.forename: C Y
authors.initials: CY
authors.lastname: Chang
authors.forename: K H
authors.initials: KH
authors.lastname: Chang
authors.forename: I C
authors.initials: IC
authors.lastname: Chen
authors.forename: M L
authors.initials: ML
authors.lastname: Li
authors.forename: G-J
authors.initials: GJ
authors.lastname: Lee-Chen
authors.forename: Y R
authors.initials: YR
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D051844:alpha-Synuclein