title: Angiogenin levels and ANG genotypes: dysregulation in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To determine whether 5 single nucleotide polymorphisms (SNPs) associate with ALS in 3 different populations. We also assessed the contribution of genotype to angiogenin levels in plasma and CSF.
  
  
  METHODS
  Allelic association statistics were calculated for polymorphisms in the ANG gene in 859 patients and 1047 controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin levels were quantified and stratified according to genotypes across the ANG gene. The contribution of SNP genotypes to variance in circulating angiogenin levels was estimated in patients and controls.
  
  
  RESULTS
  All SNPs showed association with ALS in the Irish group. The SNP rs17114699 replicated in the Swedish cohort. No SNP associated in the Polish cohort. Age- and sex-corrected circulating angiogenin levels were significantly lower in patients than in controls (p<0.001). An allele dose-dependent regulation of angiogenin levels was observed in controls. This regulation was attenuated in the ALS cohort. A significant positive correlation between CSF plasma angiogenin levels was present in controls and abolished in ALS.
  
  
  CONCLUSIONS
  ANG variants associate with ALS in the Irish and Swedish populations, but not in the Polish. There is evidence of dysregulation of angiogenin expression in plasma and CSF in sporadic ALS. Angiogenin expression is likely to be important in the pathogenesis of ALS.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland. mclaugr@tcd.ie
authors.forename: Russell Lewis
authors.initials: RL
authors.lastname: McLaughlin
authors.forename: Julie
authors.initials: J
authors.lastname: Phukan
authors.forename: William
authors.initials: W
authors.lastname: McCormack
authors.forename: David S
authors.initials: DS
authors.lastname: Lynch
authors.forename: Matthew
authors.initials: M
authors.lastname: Greenway
authors.forename: Simon
authors.initials: S
authors.lastname: Cronin
authors.forename: Jean
authors.initials: J
authors.lastname: Saunders
authors.forename: Agnieska
authors.initials: A
authors.lastname: Slowik
authors.forename: Barbara
authors.initials: B
authors.lastname: Tomik
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
authors.forename: Phil
authors.initials: P
authors.lastname: Jakeman
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
mesh_terms: D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D015810:Linkage Disequilibrium; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012259:Ribonuclease, Pancreatic / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D013548:Sweden
chemical_list: C046366:angiogenin; D012259:Ribonuclease, Pancreatic