Publication:

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.