title: Association of paraoxonase gene cluster polymorphisms with ALS in France, Quebec, and Sweden.
abstract: 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.affiliation: Center of Excellence in Neuromics, University of Montreal, CHUM Research Center, Notre-Dame Hospital, Montreal, Quebec, Canada.
authors.forename: P N
authors.initials: PN
authors.lastname: Valdmanis
authors.forename: E
authors.initials: E
authors.lastname: Kabashi
authors.forename: A
authors.initials: A
authors.lastname: Dyck
authors.forename: P
authors.initials: P
authors.lastname: Hince
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Dion
authors.forename: M
authors.initials: M
authors.lastname: D'Amour
authors.forename: F
authors.initials: F
authors.lastname: Souchon
authors.forename: J-P
authors.initials: JP
authors.lastname: Bouchard
authors.forename: F
authors.initials: F
authors.lastname: Salachas
authors.forename: V
authors.initials: V
authors.lastname: Meininger
authors.forename: P M
authors.initials: PM
authors.lastname: Andersen
authors.forename: W
authors.initials: W
authors.lastname: Camu
authors.forename: N
authors.initials: N
authors.lastname: Dupré
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D005260:Female; D005602:France; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D013548:Sweden
chemical_list: D043303:Aryldialkylphosphatase