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SERPINA 1 and MAN 1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha‐1 antitrypsin deficiency children
Author(s) -
Joly Philippe,
Lachaux Alain,
Ruiz Mathias,
Restier Lioara,
Belmalih Abdelhouaed,
ChapuisCellier Colette,
Francina Alain,
Renoux Céline,
Bouchecareilh Marion
Publication year - 2017
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13586
Subject(s) - haplotype , snp , genotype , allele , cohort , genetics , liver disease , disease , gene , medicine , biology , single nucleotide polymorphism
Background & Aims Fifteen to twenty percent of alpha‐1 antitrypsin deficiency patients (A1 ATD ) have a severe liver outcome (portal hypertension ‐ PHT ) during childhood. Since they all share the same ZZ SERPINA 1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNP s located on the SERPINA 1 and MAN 1B1 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 SERPINA 1 and MAN 1B1 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 SERPINA 1 and another for MAN 1B1 ) were not confirmed in our cohort. Moreover, the haplotype analysis identified only one major genetic background for the SERPINA 1 Z‐allele, allowing us to exclude the presence of a frequent modifier SNP within. For MAN 1B1 , 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 A1 ATD .