Angiogenin Levels and ANG Genotypes: Dysregulation in Amyotrophic Lateral Sclerosis

Abstract

ObjectiveTo 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.MethodsAllelic 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.ResultsAll 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.

The Potential of Angiogenin as a Serum Biomarker for Diseases: Systematic Review and Meta-Analysis

“…For example, Montero et al reported that serum ANG concentrations were significantly elevated in patients with breast cancer [ 11 ]; however, others did not observe this phenomenon [ 12 – 14 ]. Two of three studies investigating the association between serum ANG levels and amyotrophic lateral sclerosis (ALS) reported that serum ANG levels were elevated in affected patients compared with those in control subjects [ 15 , 16 ]; however, the other study drew the opposite conclusion [ 17 ]. These inconsistent results may be attributable to the limited numbers of subjects, as well as to small differences between the patients and healthy controls enrolled in each study.…”

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin and controls its growth and survival activities

“…In contrast to its upregulation in various cancers, ANG is downregulated in amyotrophic lateral sclerosis (ALS) (McLaughlin et al, 2010), Parkinson's disease (PD) (Steidinger et al, 2011) and Alzheimer's disease (Kim and Kim, 2012). More importantly, loss-of-function mutations have been found in patients with ALS and PD (Conforti et al, 2008;Gellera et al, 2008;Greenway et al, 2006;Paubel et al, 2008;van Es et al, 2009;Wu et al, 2007).…”

A Novel Methodology for Structural, Functional and Toxicological Analysis of Mutant Angiogenin Protein in Human

“…ANG plays important role in number of pathogenic conditions including cancer and neurodegenerative diseases by modulating cell growth and survival properties [2]. In contrast to being up regulated in cancer, ANG is down regulated in neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson and Alzheimer disease [3][4][5]. Role of ANG in neurodegenerative diseases have been documented due to function lose mutations found in patients [6,7].…”