A Particular SORL1 Micro-haplotype May Prevent Severe Liver Disease in a French Cohort of Alpha 1-Antitrypsin-deficient Children.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
pubmed:
16
3
2021
medline:
26
10
2021
entrez:
15
3
2021
Statut:
ppublish
Résumé
The presence of modifier genes is now well recognized in severe liver disease outcome associated with alpha-1-antitrypsin deficiency (A1ATD) but their identification remains to be fully elucidated. To address this goal, we performed a candidate gene study with the SORL1 gene, already identified as risk gene in early-onset Alzheimer Disease families. A particular SORL1 micro-haplotype constituted with 3 SNPs (wild-type form TTG) was genotyped on 86 ZZ A1ATD children issued from 66 families. Interestingly, the mutated forms of this micro-haplotype (CAT most of the time) were associated with lower occurrence of severe liver disease and in cellulo studies showed that SORL1 influences Z-A1ATD cellular toxicity and biogenesis. These data suggest that the mutated CAT form of SORL1 micro-haplotype may partly prevent from severe liver disease in A1ATD children. Overall, these findings support a replication study on an independent cohort and additional in cellulo studies to confirm these promising results.
Identifiants
pubmed: 33720088
doi: 10.1097/MPG.0000000000003125
pii: 00005176-202109000-00022
doi:
Substances chimiques
LDL-Receptor Related Proteins
0
Membrane Transport Proteins
0
SORL1 protein, human
0
alpha 1-Antitrypsin
0
Banques de données
ClinicalTrials.gov
['NCT01862211']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e68-e72Informations de copyright
Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet 2005; 365:2225–2236.
Sveger T. The natural history of liver disease in alpha 1-antitrypsin deficient children. Acta Paediatr Scand 1988; 77:847–851.
Ruiz M, Lacaille F, Berthiller J, et al. Groupe Francophone d’Hépatologie Gastroentérologie et Nutrition Pédiatriques. Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort. Liver Int 2019; 39:1136–1146.
Chappell S, Hadzic N, Stockley R, et al. A polymorphism of the alpha1-antitrypsin gene represents a risk factor for liver disease. Hepatology 2008; 47:127–132.
Pan S, Huang L, McPherson J, et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology 2009; 50:275–281.
Joly P, Lachaux A, Ruiz M, et al. SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children. Liver Int 2017; 37:1608–1611.
Joly P, Vignaud H, Di Martino J, et al. ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency. PLoS One 2017; 12:e0179369.
Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007; 39:168–177.
Bouchecareilh M, Hutt DM, Szajner P, et al. Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of alpha1-antitrypsin deficiency. J Biol Chem 2012; 287:38265–38278.
Hutt DM, Roth DM, Vignaud H, et al. The histone deacetylase inhibitor, Vorinostat, represses hypoxia inducible factor 1 alpha expression through translational inhibition. PLoS One 2014; 9:e106224.
Hutt DM, Roth DM, Marchal C, et al. Using histone deacetylase inhibitors to analyze the relevance of HDACs for translation. Methods Mol Biol 2017; 1510:77–91.
Scheet P, Stephens M. A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 2006; 78:629–644.
Hermey G. The Vps10p-domain receptor family. Cell Mol Life Sci 2009; 66:2677–2689.
Zhang Y, Chen K, Sloan SA, et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 2014; 34:11929–11947.
Andersen OM, Reiche J, Schmidt V, et al. Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A 2005; 102:13461–13466.
Andersen OM, Schmidt V, Spoelgen R, et al. Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry 2006; 45:2618–2628.
Fjorback AW, Seaman M, Gustafsen C, et al. Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing. J Neurosci 2012; 32:1467–1480.
Dodson SE, Gearing M, Lippa CF, et al. LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. J Neuropathol Exp Neurol 2006; 65:866–872.
Gelling CL, Dawes IW, Perlmutter DH, et al. The endosomal protein-sorting receptor sortilin has a role in trafficking alpha-1 antitrypsin. Genetics 2012; 192:889–903.
Knupp A, Mishra S, Martinez R, et al. Depletion of the AD risk gene SORL1 selectively impairs neuronal endosomal traffic independent of amyloidogenic APP processing. Cell Rep 2020; 31:107719.