Function of genetic modifiers of AATD
Research type
Research Study
Full title
Function of genetic modifiers of AATD
IRAS ID
135769
Contact name
Alice M Turner
Contact email
Sponsor organisation
University of Birmingham
Research summary
This project is designed to find out how variation in genes affects cells in the lungs and blood of patients with alpha 1 antitrypsin deficiency (AATD). Patients with AATD are prone to developing chronic obstructive pulmonary disease (COPD), but there is a wide range of disease severity seen. Studies in patients with AATD and COPD have shown that this may be due to the effect of other genes; one of those with the strongest evidence is iron regulating protein 2 (IREB2). Variations, known as SNPs, within this gene have been linked to emphysema and to worse lung function in patients. The only way we can tell how these genes affect the lungs, or whether targeting treatment towards them will help patients, is for us to look at how the cells found in the lung behave. In this project we will collect 3 cell types from the lungs of 60 patients with AATD, half of whom have the SNP in the IREB2 gene which is linked to lung disease, and half without. We will also test whether the effects of the gene are specific to AATD by studying 10 patients who have COPD without AATD and comparing them to similar AATD patients. We will match them by their IREB2 gene variant, age and lung function so that we can be confident of any differences being due to AATD. We will test whether patients who have the high risk gene are different from those without by seeing if their cells produce more inflammation, are less able to protect the lung from bacteria, or move differently. We will also see if cells behave differently when exposed to cigarette smoke and iron. We need to understand this before we can test whether drugs that alter iron regulation might help patients with AATD and COPD.
REC name
West Midlands - Solihull Research Ethics Committee
REC reference
13/WM/0333
Date of REC Opinion
9 Oct 2013
REC opinion
Further Information Favourable Opinion