Association Between SNAIL1 Gene Expression, SNAIL1 Genetic Variation, Vitamin D Receptor Gene Expression, and Vitamin-D Status Among Jordanian Asthmatic Patients.

BACKGROUND: Asthma is a chronic inflammatory airway disease influenced by genetic and environmental factors. Low vitamin-D status has been implicated in asthma severity, while polymorphisms in the SNAIL1 gene, a transcription factor involved in epithelial-mesenchymal transition, may affect airway remodeling. AIM: This exploratory study aimed to investigate the relationship between SNAIL1 genetic variants, SNAIL1 and vitamin-D receptor (VDR) gene expression, and vitamin-D status among Jordanian patients with asthma. METHODS: A case-control study was conducted involving 100 participants classified into four groups according to asthma status and vitamin-D status. Serum vitamin-D levels were measured, and SNAIL1 and VDR gene expression levels were analyzed using quantitative real-time PCR. Relative gene expression was calculated using the 2^-ΔΔCt method. SNAIL1 genetic variants were identified using PCR amplification followed by Sanger sequencing of the SNAIL1 coding exons. RESULTS: Serum vitamin-D concentrations differed significantly among the study groups (p < 0.0001). SNAIL1 expression showed higher fold changes in asthmatic participants than in non-asthmatic participants, irrespective of vitamin D status; however, these differences did not reach statistical significance (p = 0.08-0.09). VDR expression demonstrated a decreasing trend in participants with low vitamin-D status, although most comparisons were not statistically significant. A novel missense variant in SNAIL1 (c.196C>T; p.Ala66Val) was identified in a single asthmatic participant with low vitamin-D status. This participant also exhibited higher SNAIL1 expression; however, the biological significance of this observation remains exploratory. In silico prediction tools classified this variant as benign, and its potential biological significance remains exploratory. CONCLUSION: This study provides exploratory evidence suggesting potential relationships among SNAIL1 expression, VDR expression, vitamin D status, and asthma in a Jordanian population. The identified SNAIL1 variant represents a preliminary finding requiring further investigation. Larger studies with functional validation are needed to confirm these observations and provide a basis for future multidisciplinary research.