PON1 gene polymorphisms in patients with chronic obstructive pulmonary disease

J Clin Pathol. 2018 Nov;71(11):963-970. doi: 10.1136/jclinpath-2018-205194. Epub 2018 Jun 1.

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.

Keywords: -108C>T; L55M; Q192R; chronic obstructive pulmonary disease; paraoxonase 1; polymorphisms.

MeSH terms

  • Aged
  • Area Under Curve
  • Aryldialkylphosphatase / blood
  • Aryldialkylphosphatase / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • ROC Curve
  • Risk Factors

Substances

  • Aryldialkylphosphatase
  • PON1 protein, human