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

To evaluate the association of PTCH1 polymorphic variants (rs56161606 and rs41313327) with COPD susceptibility and clinical phenotypes in a North Indian population. METHODOLOGY A case-control study was conducted involving 500 COPD patients and 500 controls. Genotyping was performed on PTCH1 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

PTCH1 variants were not associated with overall COPD susceptibility. However, rs41313327 demonstrated an age-dependent effect, with the TT genotype increasing COPD risk in individuals aged ≥57 years (aOR = 1.8, p = 0.03). The rs56161606 variant was significantly associated with prolonged disease duration, increased mucus hypersecretion (aOR = 1.6, p = 0.04), exacerbation risk (aOR = 2.4, p = 0.02), and a genotype-dependent decline in the FEV1/FVC ratio (p < 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

The PTCH1 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.