SCGB1A1 rs3741240 variant downregulates CC16: a molecular insight into COPD pathogenesis in Indian population

Area of Science:

• Genetics and Respiratory Medicine
• Molecular Biology
• Bioinformatics

Background:

• Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory lung disorder with environmental and genetic influences.
• The rs3741240 polymorphism in the SCGB1A1 gene, encoding anti-inflammatory protein CC16, is a potential genetic marker for COPD susceptibility.

Purpose of the Study:

• To investigate the functional significance of the SCGB1A1 rs3741240 polymorphism in a West Bengal Indian population.
• To determine the association between this polymorphism and COPD risk, lung function, and CC16 expression.

Main Methods:

• Genotyping using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
• Quantification of SCGB1A1 mRNA and protein expression via Real-Time PCR and Western blotting.
• In silico analyses of miRNA and transcription factor interactions with the SCGB1A1 promoter.

Main Results:

• The 38AA risk genotype of rs3741240 was more prevalent in COPD patients.
• Patients with the 38AA genotype showed significantly lower FEV1 and FEV1/FVC.
• Reduced SCGB1A1 mRNA and protein expression were observed in individuals with the 38AA genotype.

Conclusions:

• The SCGB1A1 rs3741240 polymorphism is associated with COPD in an Indian population through CC16 downregulation.
• This finding reveals a key pathogenic mechanism for COPD.
• The results suggest potential for precision medicine strategies in COPD management.