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RESEARCH PRODUCT

Plasma circulating miRNAs as diagnostic and prognostic biomarkers in alpha-1 antitrypsin deficiency

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Introduction: Alpha-1 antitrypsin (AATD) deficiency is an inherited condition that leads to decreased circulating AAT levels, significantly increasing the risk of lung and liver disease. AATD is underdiagnosed. Severity of symptoms in AATD patients are highly variable and neither protein levels nor phenotype are sufficient to identify which patients will develop lung and/or liver disease. Therefore, new strategies and biomarkers for early diagnosis and prognosis of the disease are needed. Rationale and Aims: MicroRNAs (miRNAs) regulate gene expression and have been associated with the pathogenesis of various lung and liver diseases. Circulating miRNAs may serve as diagnostic and prognostic biomarkers of the AATD. This study is aimed is to determine an expression profile of plasma miRNAs in AATD to serve as a diagnostic and prognostic tool for the disease. Material and Methods: Expression profile of plasma miRNAs was determined using GeneChip miRNA 3.0 Arrays (Affymetrix) in 37 patients with DAAT and 19 healthy volunteers. Differentially expressed miRNAs were validated by RT-qPCR in 34 DAAT patients and 14 healthy volunteers. Results: A profile of differentially expressed plasma miRNAs that can potentially serve as biomarkers for the diagnosis and prognosis of AATD was identified. Specifically, miRNA-122, miR-93, miR-107, miR-425 and miR-151a miRNAs have diagnostic value, while miRNA-17, miRNA-106a and miRNA-93 are elevated in patients with emphysema and miRNA-107 and miRNA-23b are increased in patients with liver disease. Conclusions: We have identified a genetic signature that differentiates the different risk groups and the presence of emphysema and hepatopathy in AATD patients.