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

Background and Aims Fifteen to twenty percent of alpha-1 anti-trypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZ SERPINA1 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 on 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 on these two genes probably do not influence the onset of severe liver disease in A1ATD. This article is protected by copyright. All rights reserved.