Recent advancements in understanding the genetic involvement of alpha-1 antitrypsin deficiency associated lung disease: a look at future precision medicine approaches.

ABSTRACT:

Introduction

Alpha-1 antitrypsin deficiency occurs in individuals with deleterious genetic mutations on both chromosomes (maternal and paternal) in SERPINA1, the gene encoding the alpha-1 antitrypsin protein. There has been substantial progress in understanding the genetic variation that underlies the heterogeneous penetrance of lung disease in alpha-1 antitrypsin deficiency.

Areas covered

This review will cover SERPINA1 gene structure and genetic variation, population genetics, genome-wide genetic modifiers of lung disease, alternative mechanisms of disease, and emerging therapeutics - including gene and cell therapy - related to alpha-1 antitrypsin deficiency-associated lung disease.

Expert opinion

There remains ample opportunity to employ precision medicine in the diagnosis, prognosis, and therapy of alpha-1 antitrypsin deficiency-associated lung disease. In particular, a genome-wide association study and subsequent polygenic risk score is an important first step in identifying genome-wide genetic modifiers contributing to the variability of lung disease in severe alpha-1 antitrypsin deficiency.

SUBMITTER: Ghosh AJ 

PROVIDER: S-EPMC8983484 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature