University of Limerick
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Angiogenin levels and ANG genotypes: dysregulation in amyotrophic lateral sclerosis

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journal contribution
posted on 2012-07-25, 07:45 authored by Russell Lewis McLaughlin, Julie Phukan, William McCormack, David S. Lynch, Matthew Greenway, Simon Cronin, Jean Saunders, Agnieska Slowik, Barbara Tomik, Peter M. Anderson, David G. Bradley, Philip M. Jakeman, Orla Hardiman
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.


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PLoS One;5(11), e15402


Public Library of Science


peer-reviewed This paper was obtained through PEER (Publishing and the Ecology of European Research)

Other Funding information

HRB, Irish Motor Neurone Disease Research Foundation, Muscular Dystrophy Association (United States)



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