Document Detail

Association of sequence alterations in the putative promoter of RAB7L1 with a reduced parkinson disease risk.
MedLine Citation:
PMID:  22232350     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To examine whether PARK16, which was recently identified as a protective locus for Parkinson disease (PD) in Asian, white, and South American populations, is also associated with PD in the genetically homogeneous Ashkenazi Jewish population.
DESIGN: Case-control study.
SETTING: A medical center affiliated with a university. Subjects  Five single-nucleotide polymorphisms (SNPs) located between RAB7L1 and SLC41A1 were analyzed in 720 patients with PD and 642 controls, all of Ashkenazi Jewish origin.
MAIN OUTCOME MEASURES: Haplotypes were defined and risk estimates were determined for each SNP and haplotype. Bioinformatic analysis defined the putative promoter region of RAB7L1 and the transcription factor binding sites that are potentially affected by 2 of the tested SNPs.
RESULTS: All tested SNPs were significantly associated with PD (odds ratios = 0.64-0.76; P = .0002-.014). Two of them, rs1572931 and rs823144, were localized to the putative promoter region of RAB7L1 and their sequence variations altered the predicted transcription factor binding sites of CdxA, p300, GATA-1, Sp1, and c-Ets-1. Only 0.4% of patients were homozygous for the protective rs1572931 genotype (T/T), compared with 3.0% among controls (P = 5 × 10(-5)). This SNP was included in a haplotype that reduced the risk for PD by 10- to 12-fold (P = .002-.01) in all patients with PD and in a subgroup of patients who do not carry the Ashkenazi founder mutations in the GBA or LRRK2 genes.
CONCLUSIONS: Our data demonstrate that specific SNP variations and haplotypes in the PARK16 locus are associated with reduced risk for PD in Ashkenazim. Although it is possible that alterations in the putative promoter of RAB7L1 are associated with this effect, the role of other genes in this locus cannot be ruled out.
Ziv Gan-Or; Anat Bar-Shira; Dvir Dahary; Anat Mirelman; Merav Kedmi; Tanya Gurevich; Nir Giladi; Avi Orr-Urtreger
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of neurology     Volume:  69     ISSN:  1538-3687     ISO Abbreviation:  Arch. Neurol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-10     Completed Date:  2012-02-21     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  0372436     Medline TA:  Arch Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105-10     Citation Subset:  AIM; IM    
Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann St, Tel Aviv 64239, Israel.
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MeSH Terms
Aged, 80 and over
Arthritis / complications,  genetics
Binding Sites / genetics
Case-Control Studies
Computational Biology
Deafness / complications,  genetics
Gene Frequency
Genetic Predisposition to Disease
Genome-Wide Association Study*
Middle Aged
Odds Ratio
Parkinson Disease / complications,  ethnology,  genetics*
Polychondritis, Relapsing / complications,  genetics
Polymorphism, Single Nucleotide / genetics*
Promoter Regions, Genetic / genetics*
Protein-Serine-Threonine Kinases / genetics
Risk Factors
beta-Glucosidase / genetics
rab GTP-Binding Proteins / genetics*
Reg. No./Substance:
152989-05-4/rab7 protein; EC protein, human; EC Kinases; EC; EC 3.6.1.-/rab GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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