New research shows how mutations acquired throughout life can protect liver cells from damage caused by an inherited genetic condition.
Acquired DNA mutations found in the SERPINA1 gene can protect liver cells from damage in patients with alpha-1 antitrypsin deficiency, new research shows. Alpha-1 antitrypsin deficiency (A1AD) is a genetic condition caused by inherited mutations inSERPINA1, that can cause lung and liver disease.
Researchers from the Wellcome Sanger Institute and their collaborators sought to understand if acquired mutations in patients with haemochromatosis, an iron overload disorder, or alpha-1-antitrypsin deficiency offer protection against cell stress.
The study, published today (10 March 2025) in Nature Genetics, provides further understanding about how protective mutations may help inspire therapies in patients with chronic liver disease.
Patients with A1AD are born with faults in a gene called SERPINA1. These faults cause changes to a type of protein called alpha-1 antitrypsin.1 The changes make alpha-1 antitrypsin proteins stick together and form clumps inside liver cells. The protein clumps damage liver cells, increasing the risk of liver disease and can also lead to chronic obstructed pulmonary disorder (COPD).
The lung symptoms of A1AD can be medically managed and include the use of augmentation therapy2, inhaled steroids, antibiotics or intravenous infusions of alpha-1 antitrypsin protein. However, for those with associated liver disease, liver transplantation remains the only treatment option.
In the new study, Sanger Institute researchers and their collaborators explored whether mutations in the liver are disease specific.
Credit: Sanga Institute