Potential modifier genes for cystic fibrosis disease

Abstract

Background

Cystic Fibrosis (CF) is a genetic disease caused primarily by mutations in the CFTR gene. However, CF patients with the same mutations in the CFTR gene can manifest the disease with varying severity, likely due to the role of modifier genes.

Methodology

To uncover the underlying non-CFTR genetic factors, we compiled a list of CF modifier genes through an extensive literature review and conducted pathway enrichment analysis using ENRICHR and DAVID tools to understand their biological significance and functional roles in CF disease. We also used the STRING tool to explore the protein-protein interaction of genes identified by pathway enrichment analysis with the CFTR gene.

Results

The literature review identified 36 CF modifier genes: GSTM1, IL10, SLC26A9, IL1B, MUC6, CLC-2, CXCL8/IL8, EDNRA, DCTN4, SLC9A3, ADRB2, AGER, EZR, HLAII, HFE, CFTR, IFRD1, CAV1, PRKAR2B, PPP2R4, MBL2, EHF, SCNN1A, SERPINA1, AHSAI, SNAP23, SCNN1B, SCNN1G, PRSS8, SLC9A3R1/NHERF1, KRT19, Nedd4L, TGFB1, CALR, SLC6A14, MMP9 and MIF. Pathway enrichment analysis predicted three key pathways linked to CF and enriched with 13 modifier genes. Furthermore, the STRING tool predicted that six out of the thirteen modifier genes (SLC9A3R1, EZR, ADRB2, SERPINA1, IL1B, and IFRD1) interact with CFTR, indicating a complex network of functional relationships supported by various evidence.

Conclusion

This research identified 36 modifier genes associated with cystic fibrosis, alongwith three key pathways enriched with 13 of these genes. Six of these genes were found to have a complex network of interactions with CFTR genes, highlighting their probable role as CF modifier genes.