Genotyping and receiver operating characteristic-based evaluation of Paraoxonase-1 in stable chronic obstructive pulmonary disease: a case-control study from Central India

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, particularly in low- and middle-income countries like India. Oxidative stress is a key contributor to COPD pathogenesis, and the Paraoxonase 1 (PON1) enzyme plays a crucial antioxidant role. This case-control study from Central India investigated the association of PON1 gene polymorphisms-Q192R and L55M-with PON1 enzyme activity and lipid peroxidation marker malondialdehyde (MDA) in stable COPD patients. Methods: Sixty COPD patients and 60 age and sex-matched healthy controls were enrolled. PON1 activity was measured spectrophotometrically, and genotyping was performed using PCR-RFLP. Receiver operating characteristic (ROC) analysis assessed the diagnostic performance of PON1 activity. Results: COPD patients had significantly lower PON1 activity than controls (p<0.001). The RR genotype and R allele of the Q192R polymorphism were more frequent in COPD patients and associated with reduced enzyme activity (OR 2.7; p=0.02). L55M polymorphism showed no significant intergroup difference. An optimal PON1 activity cutoff of 118.2 U/l (Youden’s index) yielded 80% sensitivity and 86.7% specificity in distinguishing COPD from controls. Findings suggest the R allele and RR genotype as potential genetic risk markers for COPD, with decreased PON1 activity indicating impaired antioxidant defence. Conclusions: This is the first report of PON1 polymorphism data in COPD patients from India, offering novel insights into gene-environment interactions and genetic susceptibility. Larger studies are needed to confirm these results and assess the role of PON1 genotyping in risk stratification and disease management.