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. 2021 Sep 1;73(3):e68-e72.
doi: 10.1097/MPG.0000000000003125.

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

Philippe Joly  1   2 , Mathias Ruiz  3 , Roman Garin  1 , Esra Karatas  4 , Alain Lachaux  3 , Lioara Restier  3 , Abdelouahed Belmalih  3 , Céline Renoux  1   2 , Christine Lombard  5 , Magali Dechomet  5 , Marion Bouchecareilh  4
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Free article

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

Philippe Joly et al. J Pediatr Gastroenterol Nutr. .
Free article

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.

Trial registration: ClinicalTrials.gov NCT01862211.

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Conflict of interest statement

The authors report no conflicts of interest.

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