Genotyping and receiver operating characteristic-based evaluation of Paraoxonase-1 in stable chronic obstructive pulmonary disease: a case-control study from Central India
DOI:
https://doi.org/10.18203/2320-6012.ijrms20253152Keywords:
Praoxonase-1, Diagnostic accuracy, Stable COPD, Q192R, Oxidative stressAbstract
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.
Metrics
References
WHO. Chronic obstructive pulmonary disease (COPD). World Health Organization. 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd). Accessed on 15 July 2025.
Salvi S, Kumar GA, Dhaliwal RS. The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990-2016. Lancet Glob Health. 2018;6(12):1363-74. DOI: https://doi.org/10.1016/S2214-109X(18)30409-1
Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest. 2013;144(1):266-73. DOI: https://doi.org/10.1378/chest.12-2664
Nicks ME, O'Brien MM, Bowler RP. Plasma antioxidants are associated with chronic obstructive pulmonary disease severity and survival. COPD. 2011;8(2):144-9. DOI: https://doi.org/10.3109/15412555.2011.579202
Camps J, Marsillach J, Joven J. The paraoxonases: role in human diseases and methodological difficulties in measurement. Crit Rev Clin Lab Sci. 2009;46(2):83-106. DOI: https://doi.org/10.1080/10408360802610878
Mackness B, Durrington PN, Mackness MI. Human serum paraoxonase. Gen Pharmacol. 1998;31(3):329-36. DOI: https://doi.org/10.1016/S0306-3623(98)00028-7
Costa LG, Cole TB, Jarvik GP, Furlong CE. Functional genomics of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annu Rev Med. 2003;54:371-92. DOI: https://doi.org/10.1146/annurev.med.54.101601.152421
Sumanpreet Kaur, Gurjit Kaur Bhatti, Rajesh Vijayvergiya, Puneetpal Singh, Sarabjit Singh Mastana, Rupinder Tewari, et al. Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians. International Journal of Diabetes and Metabolism 28 December 2018; 24 (1-4): 38–47. DOI: https://doi.org/10.1159/000494508
Kumari M, Nigoskar RS. Association of Paraoxonase 1 (PON1) gene polymorphisms (Q192R and L55M) with enzyme activity and glycemic control in type 2 diabetes mellitus. Int J Acad Med Pharm. 2025;7(4):160–3.
Watanabe J, Kotani K, Gugliucci A. Paraoxonase 1 and chronic obstructive pulmonary disease: a meta-analysis. Antioxidants. 2021;10(12):1891. DOI: https://doi.org/10.3390/antiox10121891
Grdić Rajković M, Popović-Grle S, Vukić Dugac A, et al. PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease. J Clin Pathol. 2018;71(11):963-9. DOI: https://doi.org/10.1136/jclinpath-2018-205194
Gürbüz N, Yildiz M, Yildiz BS. Paraoxonase-1 gene in patients with chronic obstructive pulmonary disease: investigation of Q192R and L55M polymorphisms. World J Emerg Med. 2015;6(3):217–22. DOI: https://doi.org/10.5847/wjem.j.1920-8642.2015.03.007
Solmaz Avcikurt A, Gencer N, Yazici H. Q192R polymorphism in the PON1 gene and nasal polyp in a Turkish population. J Biochem Mol Toxicol. 2021;35(12):e22628. DOI: https://doi.org/10.1002/jbt.22628
Dutta T, Bhattacharya A. Chronic obstructive pulmonary disease (COPD): making sense of existing GWAS findings in Indian context. ResearchGate; 2022. DOI: https://doi.org/10.61797/ijbca.v2i1.163
Tekin D. Oxidative stress and antioxidant defense in COPD: The role of paraoxonase-1 polymorphisms. Respir Med. 2020;171:106090.
Kamal MM. Paraoxonase 1 activity and gene polymorphisms in chronic obstructive pulmonary disease: A meta-analysis. Biomed Pharmacother. 2022;146:112601.
Ibrahim MA. Genetic polymorphism of paraoxonase-1 and its association with oxidative stress in COPD patients. Lung India. 2022;39(1):24-9. DOI: https://doi.org/10.4103/0970-2113.44194