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Angiogenin levels and ANG genotypes: dysregulation in amyotrophic lateral sclerosis.
McLaughlin, Russell Lewis Phukan, Julie McCormack, William Lynch, David S Greenway, Matthew Cronin, Simon Saunders, Jean Slowik, Agnieska Tomik, Barbara Andersen, Peter M
McLaughlin, Russell Lewis
Phukan, Julie
McCormack, William
Lynch, David S
Greenway, Matthew
Cronin, Simon
Saunders, Jean
Slowik, Agnieska
Tomik, Barbara
Andersen, Peter M
Advisors
Editors
Other Contributors
Date
2010-11
Date Submitted
Keywords
Other Subjects
Subject Mesh
Alleles
Amyotrophic Lateral Sclerosis
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Ireland
Linkage Disequilibrium
Poland
Polymorphism, Single Nucleotide
Ribonuclease, Pancreatic
Sweden
Amyotrophic Lateral Sclerosis
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Ireland
Linkage Disequilibrium
Poland
Polymorphism, Single Nucleotide
Ribonuclease, Pancreatic
Sweden
Planned Date
Start Date
Collaborators
Principal Investigators
Files
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21085671.pdf
Adobe PDF, 555.92 KB
Alternative Titles
Publisher
Abstract
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.
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.
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.
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.
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.
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.
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.
Language
en
ISSN
1932-6203
eISSN
ISBN
DOI
10.1371/journal.pone.0015402
PMID
21085671