Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma

Chest. 2007 Jul;132(1):120-6. doi: 10.1378/chest.07-0371. Epub 2007 May 2.

Abstract

Background: Cytochrome P-450 2J2 (CYP2J2) has recently been shown to be an important enzyme in the metabolism of epoxygenase-derived eicosanoids that play important functional roles in pulmonary physiology and may contribute to the pathogenesis of asthma.

Study objective: The focus of our pilot study was to evaluate whether common polymorphism G-50T within the proximal promoter of human CYP2J2 gene is associated with the susceptibility to bronchial asthma.

Design and participants: A total of 429 unrelated Russian subjects were recruited in this case-control study, including 215 sex-matched and age-matched patients with asthma and 214 healthy control subjects. The blood samples were analyzed for genetic polymorphism G-50T in the CYP2J2 gene by polymerase chain reaction followed by restriction fragment length polymorphism analysis.

Results: The frequency of variant allele -50T of the CYP2J2 gene was significantly higher in asthmatic patients than in healthy subjects (odds ratio [OR], 5.04; 95% confidence interval [CI], 1.99 to 12.77; p = 0.0003). In addition, the heterozygous genotype -50GT of the CYP2J2 gene was found to be significantly associated with susceptibility to allergic asthma (OR, 5.40; 95% CI, 2.05 to 14.26; p = 0.0003) as well as nonallergic asthma (OR, 5.77; 95% CI, 1.84 to 18.10; p = 0.004). The associations of the CYP2J2 gene G-50T polymorphism with asthma remained significant after adjustment for age and gender using multiple logistic regression analysis.

Conclusions: Our data demonstrate for the first time that the CYP2J2 gene might be considered as a novel candidate gene for common susceptibility to asthma and highlight the importance of the P-450 epoxygenase pathway of metabolism of arachidonic acid in the pathogenesis of the disease.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Arachidonic Acid / metabolism
  • Asthma / enzymology
  • Asthma / genetics*
  • Case-Control Studies
  • Cytochrome P-450 CYP2J2
  • Cytochrome P-450 Enzyme System / genetics*
  • Eicosanoids / metabolism
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Oxygenases / genetics*
  • Pilot Projects
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*

Substances

  • CYP2J2 protein, human
  • Eicosanoids
  • Arachidonic Acid
  • Cytochrome P-450 Enzyme System
  • Oxygenases
  • Cytochrome P-450 CYP2J2