(P21-017-25) Dysregulation of Zinc Transporters in Alpha-1 Antitrypsin Deficiency

Objectives: Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, which can result in liver disease or lung disease, or both. We carried out in silico analysis of the mRNA expression of genes involved in zinc metabolism in liver samples from mice overexpressing mutant human SERPINA1 (ATZ) (PiZ mice). In addition, the expression of these genes in lung samples from patients with AATD and controls was analyzed.

Methods: Data was extracted from the following series from Gene Expression Omnibus (GEO): GSE141593, GSE93115, GSE179416, GSE36478, and GSE1122 The mRNA expression of the zinc transporter gene families of SLC30A and SLC39A, MTF1 gene (Metal Regulatory Transcription Factor 1), and metallothionein 1 through 4 (MTs) was examined. Student t-test was used to analyze the data (P < 0.05). Furthermore, differential expression analysis was conducted to determine down or up regulation of gene expression.

Results: Some GEO DataSet series did not provide data for some Slc30a, Slc39a, and MTF1, and MTs genes. There was overall statistical significance with different SlC30aand Slc39a genes which suggests zinc metabolism dysregulation in both liver and lung samples. There did not seem to be a particular gene expressing statistical significance in all investigated GEO DataSet series obtained from liver samples. Overall, the higher prevalence genes with of statistical significance (p < 0.05) seems to be within the Slc39a gene family.

Conclusions: AATD could lead to dysregulation of zinc metabolism. Further studies on the role of zinc in lung and liver diseases associated with AATD are warranted.

Funding Sources: No funding source