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Original Research: ASTHMA |

Promoter Polymorphism G-50T of a Human CYP2J2 Epoxygenase Gene Is Associated With Common Susceptibility to Asthma*

Alexey V. Polonikov, MD, PhD; Vladimir P. Ivanov, MD, PhD; Mariya A. Solodilova, PhD; Irina V. Khoroshaya, PhD; Mikhail A. Kozhuhov, PhD; Valery I. Panfilov, PhD
Author and Funding Information

*From the Department of Medical Biology, Genetics, and Ecology (Drs. Polonikov, Ivanov, Solodilova, and Khoroshaya), Kursk State Medical University, Kursk, Russia; and the Department of Pulmonology (Drs. Kozhuhov and Panfilov), Kursk Regional Clinical Hospital, Kursk, Russia.

Correspondence to: Alexey V. Polonikov, MD, PhD, Kursk State Medical University, Karl Marx St, 3, Kursk, Russia 305041; e-mail: polonikov@rambler.ru



Chest. 2007;132(1):120-126. doi:10.1378/chest.07-0371
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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.

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