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Original article
PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease
  1. Marija Grdić Rajković1,
  2. Sanja Popović-Grle2,3,
  3. Andrea Vukić Dugac2,3,
  4. Dunja Rogić1,4,
  5. Ivana Rako4,
  6. Margareta Radić Antolić4,
  7. Mirela Beriša1,
  8. Lada Rumora1
  1. 1 Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia
  2. 2 Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia
  3. 3 School of Medicine, University of Zagreb, Zagreb, Croatia
  4. 4 Clinical Institute of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia
  1. Correspondence to Professor Lada Rumora, Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia; lrumora{at}pharma.hr

Abstract

Aims Chronic obstructive pulmonary disease (COPD) is characterised with oxidative stress. Paraoxonase 1 (PON1) is an enzyme, coded by PON1 gene, with distinctive antiatherogenic and antioxidative roles. We aimed to investigate the frequencies of Q192R, L55M and −108C>T polymorphisms and association of those polymorphisms with paraoxonase and arylesterase activities in patients with COPD.

Methods PON1 genotype was determined by PCR–restriction fragment length polymorphism method. PON1 activity was measured by paraoxon and phenylacetate.

Results Only −108C>T polymorphism resulted in significantly different distribution of genotypes and alleles, with higher frequency of TT genotype and T allele in patients compared with control subjects. Moreover, T allele (OR 2.29 (95% CI 1.54 to 3.41); p<0.001) as well as TT genotype (OR 5.00 (95% CI 2.19 to 11.43); p<0.001) showed an association with the disease. −108C>T polymorphism was suggested as a significant diagnostic predictor for the disease (OR (95% CI) 2.65 (1.53 to 4.59), p=0.001), with an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84 to 0.93) and with 83.90% of correctly classified cases.

Conclusions Higher frequency of TT genotype and T allele could contribute to the observed reduction of PON1 activity in patients with COPD. T allele and TT genotype are associated with COPD, and the PON1−108C>T polymorphism could be a potential predictor of the disease.

  • chronic obstructive pulmonary disease
  • paraoxonase 1
  • polymorphisms
  • Q192R
  • L55M
  • -108C>T

https://doi.org/10.1136/jclinpath-2018-205194

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    Footnotes

    • Handling editor Runjan Chetty.

    • Contributors MGR: contributed to the conception and design of the work, analysis and interpretation of data, performed analysis of polymorphisms, drafting the work until the final version. SP-G: recruitment of healthy subjects and patients with COPD, spirometry analysis. AVD: recruitment of healthy subjects and patients with COPD, spirometry analysis. DR: contributed to the conception of the work and revising the work critically. IR: collecting and preparing the blood samples for analysis. MRA: collecting and preparing the blood samples for analysis. MB: performed analysis of polymorphisms. LR: contributed to the conception and design of the work, analysis and interpretation of data, performed analysis of polymorphisms, drafting the work until the final version.

    • Funding This work has been fully supported by the Croatian Science Foundation under the project number IP-2014-09-1247.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Ethics Committee of the University Hospital Centre Zagreb (Zagreb, Croatia) and the Committee for Ethics of Experimental Work of the Faculty of Pharmacy and Biochemistry, University of Zagreb.

    • Provenance and peer review Not commissioned; externally peer reviewed.