Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma.
| Autor: | Polonikov AV; Kursk State Medical University, Karl Marx St 3, Kursk, Russia 305041. polonikov@rambler.ru, Ivanov VP, Solodilova MA, Khoroshaya IV, Kozhuhov MA, Panfilov VI |
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| Jazyk: | angličtina |
| Zdroj: | Chest [Chest] 2007 Jul; Vol. 132 (1), pp. 120-6. Date of Electronic Publication: 2007 May 02. |
| DOI: | 10.1378/chest.07-0371 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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