A Particular SORL1 Micro-haplotype May Prevent Severe Liver Disease in a French Cohort of Alpha 1-Antitrypsin-deficient Children.

Autor: Joly P; UF « Biochimie des pathologies érythrocytaires », Laboratoire de Biochimie et Biologie moléculaire Grand-Est, Groupement hospitalier Est, Hospices Civils de Lyon, Bron.; Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Equipe 'Biologie vasculaire et du globule rouge', Université Claude Bernard Lyon 1, COMUE Lyon., Ruiz M; Department of Paediatric Gastroenterology, Hepatology and Nutrition, Reference Center for Rare Disease - Biliary Atresia And Genetic Cholestasis, Children's Hospital of Lyon, Lyon., Garin R; UF « Biochimie des pathologies érythrocytaires », Laboratoire de Biochimie et Biologie moléculaire Grand-Est, Groupement hospitalier Est, Hospices Civils de Lyon, Bron., Karatas E; INSERM, CNRS University Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, Bordeaux., Lachaux A; Department of Paediatric Gastroenterology, Hepatology and Nutrition, Reference Center for Rare Disease - Biliary Atresia And Genetic Cholestasis, Children's Hospital of Lyon, Lyon., Restier L; Department of Paediatric Gastroenterology, Hepatology and Nutrition, Reference Center for Rare Disease - Biliary Atresia And Genetic Cholestasis, Children's Hospital of Lyon, Lyon., Belmalih A; Department of Paediatric Gastroenterology, Hepatology and Nutrition, Reference Center for Rare Disease - Biliary Atresia And Genetic Cholestasis, Children's Hospital of Lyon, Lyon., Renoux C; UF « Biochimie des pathologies érythrocytaires », Laboratoire de Biochimie et Biologie moléculaire Grand-Est, Groupement hospitalier Est, Hospices Civils de Lyon, Bron.; Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Equipe 'Biologie vasculaire et du globule rouge', Université Claude Bernard Lyon 1, COMUE Lyon., Lombard C; Laboratoire d'immunologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France., Dechomet M; Laboratoire d'immunologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France., Bouchecareilh M; INSERM, CNRS University Bordeaux, UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, Bordeaux.
Jazyk: angličtina
Zdroj: Journal of pediatric gastroenterology and nutrition [J Pediatr Gastroenterol Nutr] 2021 Sep 01; Vol. 73 (3), pp. e68-e72.
DOI: 10.1097/MPG.0000000000003125
Abstrakt: Abstract: 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.
Competing Interests: The authors report no conflicts of interest.
(Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
Databáze: MEDLINE
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