| Association of paraoxonase gene cluster polymorphisms with ALS in France, Quebec, and Sweden. | |
| | |
MedLine Citation:
|
PMID: 18695162 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: The paraoxonase gene cluster on chromosome 7 comprising the PON1-3 genes is an attractive candidate for association in amyotrophic lateral sclerosis (ALS) given the role of paraoxonase genes during the response to oxidative stress and their contribution to the enzymatic break down of nerve toxins. Oxidative stress is considered one of the mechanisms involved in ALS pathogenesis. Evidence for this includes the fact that mutations of SOD1, which normally reduce the production of toxic superoxide anion, account for 12% to 23% of familial cases in ALS. In addition, PON variants were shown to be associated with susceptibility to ALS in several North American and European populations. METHODS: We extended this analysis to examine 20 single nucleotide polymorphisms (SNPs) across the PON gene cluster in a set of patients from France (480 cases, 475 controls), Quebec (159 cases, 95 controls), and Sweden (558 cases, 506 controls). RESULTS: Although individual SNPs were not considered associated on their own, a haplotype of SNPs at the C-terminal portion of PON2 that includes the PON2 C311S amino acid change was significant in the French (p value 0.0075) and Quebec (p value 0.026) populations as well as all three populations combined (p value 1.69 x 10(-6)). Stratification of the samples showed that this variation was pertinent to ALS susceptibility as a whole, and not to a particular subset of patients. CONCLUSIONS: These findings contribute to the increasing weight of evidence that genetic variants in the paraoxonase gene cluster are associated with amyotrophic lateral sclerosis. |
| | |
Authors:
|
P N Valdmanis; E Kabashi; A Dyck; P Hince; J Lee; P Dion; M D'Amour; F Souchon; J-P Bouchard; F Salachas; V Meininger; P M Andersen; W Camu; N Dupré; G A Rouleau |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Neurology Volume: 71 ISSN: 1526-632X ISO Abbreviation: Neurology Publication Date: 2008 Aug |
Date Detail:
|
Created Date: 2008-08-12 Completed Date: 2008-10-14 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0401060 Medline TA: Neurology Country: United States |
Other Details:
|
Languages: eng Pagination: 514-20 Citation Subset: AIM; IM |
Affiliation:
|
Center of Excellence in Neuromics, University of Montreal, CHUM Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amyotrophic Lateral Sclerosis
/
genetics* Aryldialkylphosphatase / genetics* Female France Genotype Haplotypes Humans Male Middle Aged Multigene Family* Polymorphism, Single Nucleotide* Quebec Sweden |
| Chemical | |
Reg. No./Substance:
|
EC 3.1.8.1/Aryldialkylphosphatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Physical frailty in older persons is associated with Alzheimer disease pathology.
Next Document: Failure of atorvastatin to modulate CSF HIV-1 infection: results of a pilot study.