Poster Presentation AUS-oMicS 2025

Genetic Polymorphisms and Pain Perception in Cystic Fibrosis: an in-silico analysis (#209)

Anastasia L Ward 1 , Ramil Mauleon 1 2 , Chee Y Ooi 3 4 , Nedeljka Rosic 1
  1. Faculty of Health, Southern Cross University, Coolangatta, QLD, Australia
  2. International Rice Research Institute, Los Banos, Laguna, Philippines
  3. Discipline of Paediatrics & Child Health, Randwick Clinical Campus, School of Clinical Medicine, UNSW Medicine & Health, Sydney, New South Wales, Australia
  4. Department of Gastroenterology, Sydney Children's Hospital Randwick, Randwick, New South Wales, Australia

Background: Cystic fibrosis (CF) is the most lethal monogenic autosomal recessive disease in Caucasians with diverse and extensive comorbidities. Where the majority of studies have focussed on the respiratory and digestive systems, there has been a paucity of research focusing on pain, even though people living with CF have reported a high prevalence and increased severity of pain. Many studies have identified the complex relationship between genotype and phenotype, and growing evidence suggests that the phenotypic variation observed not only depends on the variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene but also on modifier genes. Modifier genes have been reported to affect many organs or systems in CF. However, there have been no studies on how modifier genes may influence pain. Therefore, this study explored some modifier genes that may affect pain perception in CF.

Methods: The bioinformatics workflow adopted includes database and literature mining, pathway enrichment analysis, protein-protein interactions evaluation and drug-gene network investigation.

Results: We identified seven potential pain modifiers in CF, including Chymotrypsin C (CTRC), Serine Protease Inhibitor Kazal-type 1 (SPINK1), Tumour Necrosis Factor (TNF), ATP Binding Cassette Subfamily B Member 1 (ABCB1), Protease Serine 1 (PRSS1), Transforming Growth Factor Beta 1 (TGFB1) interacting with the CFTR gene. The analysis of the biochemical pathways indicates that signal transduction and the immune system are likely to be involved in pain processes. The specific GMs, TNF and ABCB1, are within the central hub genes, indicating that they may influence the pain pathway in CF.

Conclusions: This in-silico analysis highlights potential genes and biochemical pathways implicated in pain pathways that could significantly impact pain perception in people living with CF. Functional analyses are needed to include CF participants and provide a physiological relevance on how genetic polymorphisms of identified gene modifiers may impact their pain phenotype profile.