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Liver Int. 2017 Nov;37(11):1608-1611. doi: 10.1111/liv.13586. Epub 2017 Sep 15.

SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children.

Author information

1
Laboratoire de Biochimie et Biologie Moléculaire Grand-Est, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
2
Inter-University Laboratory of Human Movement Science, Univ Lyon - University Claude Bernard Lyon 1 - EA 7424, Villeurbanne, France.
3
Department of Paediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Lyon, Lyon, France.
4
Laboratoire d'immunologie, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France.
5
Université de Bordeaux-Institut de Biochimie et Génétique Cellulaires, Bordeaux, France.
6
France CNRS-UMR5095 Bordeaux, Bordeaux Cedex, France.
7
INSERM, UMR1053 Bordeaux Research In Translational Oncology, Univ. Bordeaux, BaRITOn, Bordeaux, France.

Abstract

BACKGROUND & AIMS:

Fifteen to twenty percent of alpha-1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results.

METHODS:

Our genotype-phenotype correlation study, performed on 92 ZZ children, aimed at determining once and for all if SERPINA1 and MAN1B1 polymorphisms may be implied in the onset of PHT. To do so, we also performed for the first time a complete haplotype reconstruction for data analysis.

RESULTS:

The two genetic associations with severe liver disease that had been suspected previously (one SNP for SERPINA1 and another for MAN1B1) were not confirmed in our cohort. Moreover, the haplotype analysis identified only one major genetic background for the SERPINA1 Z-allele, allowing us to exclude the presence of a frequent modifier SNP within. For MAN1B1, four major haplotypes were identified but the prevalence of PHT did not significantly differ between them.

CONCLUSION:

We conclude that genetic polymorphisms in these two genes probably do not influence the onset of severe liver disease in A1ATD.

KEYWORDS:

MAN1B1 ; SERPINA1 ; alpha-1 antitrypsin liver disease; modifier genes

PMID:
28887821
DOI:
10.1111/liv.13586
[Indexed for MEDLINE]

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