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Research Project

Validation of candidate genetic variants associated with liver disease in ZZ - AATD patients (Study Liver-Genetic)

Principal Investigator:
Juan Luis Rodriguez-Hermosa
Center:
Instituto de Investigación Sanitaria San Carlos/Hospital Clínico San Carlos.
City/Country:
Madrid (Spain)
Start date:
March 2025
Status:
Design
Contact E-mail:
jlrhermosa@yahoo.es
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Introduction

The genetic factors that may determine the development of liver disease in certain patients while others with the same genotype (ZZ) only develop lung disease are unknown. Whole exome genetic association analysis has identified genetic variants in genes, other than SERPINA1, potentially determining increased risk for liver disease among ZZ patients. Previous studies have selected nine genetic variants that have been found to be significantly associated with the development of lung disease and 7 variants associated with liver disease in patients with AATD ZZ. We wish to validate these results by collecting AATD samples  from EARCO to be used as a validation set.

 

Objectives

To validate the significance of 16 selected SNPs through genotyping of these variants in larger series of patients to confirm its role as risk factors for increased risk of developing liver disease

Inclusion criteria

Centres with registered cases of AATD individuals with liver disease will be asked to participate.

Brief summary

DNA will be extracted from dry blood spots from patients following standard methods and each specific variant will be genotyped Allelic frequencies of the variants will be calculated separately in ZZ patients with liver disease and ZZ patients with pulmonary disease and compared between them and with the allele frequency in the general population (obtained from gnomAD database).

 Correlation between the SNPs and clinical parameters will be evaluated applying logistic regression, and the results adjusted for confounding factors such as age and sex.

Significant results will be used to build a polygenic risk score model (PRS) to assess the genetic predisposition of a ZZ individual to develop liver disease based on the sum of effects of selected genetic variants and clinical parameters.