Role of PTCH1 receptor polymorphisms in the SHH signalling pathway as determinants of COPD severity and functional impairment

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial disorder influenced by environmental exposures and genetic factors. The Hedgehog signaling pathway, particularly the PTCH1 receptor, plays a critical role in lung development, epithelial repair, and airway remodeling. However, its genetic contribution to COPD remains unclear. OBJECTIVE: polymorphic variants (rs56161606 and rs41313327) with COPD susceptibility and clinical phenotypes in a North Indian population. METHODOLOGY: polymorphic variants (rs56161606 and rs41313327) using PCR-RFLP. Logistic regression was applied, adjusting for age, sex, and smoking. Genotype-phenotype associations were assessed using spirometric parameters, GOLD-COPD classification, and COPD symptoms. RESULTS: < 0.05), suggesting its role in airflow obstruction. Furthermore, rs56161606 exhibited phenotype-specific associations with dyspnea and physical activity, highlighting its potential influence on the clinical heterogeneity of COPD. CONCLUSION: rs56161606 polymorphism did not correlate with overall COPD susceptibility but appeared to be a possible genetic modulator of disease severity, affecting pulmonary function and phenotype-specific clinical symptoms. These results highlight the significance of Hedgehog signaling in airway remodeling and tissue repair mechanisms that contribute to the clinical heterogeneity of COPD.