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Public Library of Science, PLoS ONE, 11(5), p. e15402, 2010

DOI: 10.1371/journal.pone.0015402

Elsevier, Electoral Studies, 1(30), p. 4-15

DOI: 10.1016/j.electstud.2010.09.017

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Angiogenin Levels and ANG Genotypes: Dysregulation in Amyotrophic Lateral Sclerosis

Journal article published in 2010 by Russell Lewis Mclaughlin ORCID, Julie Phukan, William McCormack, David S. Lynch, Matthew Greenway, Jean Saunders, Simon Cronin, Agnieska Slowik, Simon Hix, Barbara Tomik, Peter M. Anderson, Peter M. Andersen, Daniel Gerard Mary Bradley ORCID, Phil Jakeman, Orla Hardiman and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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. ; peer-reviewed ; This paper was obtained through PEER (Publishing and the Ecology of European Research) http://www.peerproject.eu