Sara Gil Martín

Genetic susceptibility to liver or lung disease in AATD patients

Project's abstract and aims

Alpha-1 antitrypsin deficiency (AATD) is a genetic condition leading to both liver and lung disease, but the factors that determine why certain ZZ patients develop liver disease while others only develop lung disease remain unknown. Combination of specific variants in the genetic background of an individual may be predisposing to the development of liver or lung disease. Previous results of a whole-exome genetic association analysis performed by our group allowed us to select genetic variants with a role as genetic modifiers of the disease. A preliminary genetic association study revealed significant SNPs associated mainly with liver disease but also with lung damage. Thus, we established a Polygenic Risk Score (PRS) model including genotype information and clinical variables, able to predict which patients would develop liver disease among ZZ AATD patients.

To date, there are no reliable predictors to identify which AATD patients will develop liver disease, making individualized risk assessment an important consideration. With this project our aims are:

1. To validate selected SNPs involved in the differential development of either liver or lung damage in a larger group of AATD patients
2. To develop a PRS model to help identifying ZZ AATD patients with higher risk of liver or lung disease.
3. To design an online tool or mobile app, named POLYRISK-LD, to assist in genetic risk assessment in the clinical practice.

Biography

Sara Gil Martín has a degree in Genetics from the Autonomous University of Barcelona and a Master's degree in Translational Medicine Research from the Complutense University of Madrid. She joined the Hereditary Endocrine Cancer Group at the Spanish National Cancer Research Centre (CNIO) for the Master’s thesis working on the mutational characterisation of a series of samples to identify both driver mutations of the disease and mutations in other pathways relevant to disease progression.

Currently she is working on her PhD thesis at the Molecular Genetics Unit of the Institute of Rare Diseases Research (IIER), at the Institute of Health Carlos III (ISCIII), with a pre-doctoral contract from CIBERER. She works on the study of Alpha-1 Antitrypsin Deficiency (AATD) using hepatic cell lines and both pulmonary and hepatic organoids as disease models. Her thesis project focuses on the characterisation of the cellular and metabolic processes altered in the disease and on the study of the mutational landscape of genes related to the predisposition of AATD patients to develop either lung or liver disease.