Abstract
Frequencies of CYP1A1, CYP2E1, and mEPHX polymorphic variants were analyzed in cystic fibrosis, chronic obstructive lung disease, bronchiectatic disease, chronic nonobstructive bronchitis, and recurring bronchitis. Mutations in CYP1A1 and mEPHX were shown to modify the severity of respiratory disorders in cystic fibrosis, the combination of CYP1A1 genotype Val/Val with the “very slow” mEPHX phenotype being most unfavorable (odds ratio OR = 12.30). Heterozygosity at both CYP1A1 and CYP2E1 was associated with chronic obstructive lung disease and recurring bronchitis (OR = 4.08 and 11.72, respectively). The “very slow” phenotype of mEPHX was predisposing to chronic respiratory disorders regardless of the CYP1A1 or CYP2E1 alleles (OR = 4.06). Basing on the above correlations, a combination of the “very slow” mEPHX phenotype with elevated cytochrome P450 (CYP1A1 and CYP2E1) activities was assumed to expedite severe respiratory disorders.
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REFERENCES
Kulinskii V.I. 1999. Detoxification of xenobiotics. Soros. Obrazovat. Zh. 1, 8–12.
Baranov V.S., Baranova E.V., Ivashchenko T.E., Aseev M.V. 2000. Genom cheloveka i geny “predra-spolozhennosti” (Vvedenie v prediktivnuyu meditsinu) (The Human Genome and “Predisposition” Genes (Introduction to Predictive Medicine)). St. Petersburg: Intermedika.
Bartsch H., Nair U., Risch A. et al. 2000. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol. Biomarkers Prevention. 9, 3–28.
Huang C.-Y., Huang K.-L., Cheng T.-J. et al. 1997. The GSTT1 and CYP2E1 genotypes are possible factors causing vinyl chloride induced abnormal liver function. Arch. Toxicol. 71, 482–488.
Chuchalin A.G. 1999. Khronicheskie obstruktivnye bolezni legkikh (Chronic Obstructive Lung Diseases). Moscow: Binom.
www.goldcopd.com (Global initiative for chronic obstructive lung disease (GOLD)). 2001.
Sandford A.J., Silverman E.K. 2002. Chronic obstructive pulmonary disease. 1: Susceptibility factors for COPD the genotype-environment interaction. Thorax. 57, 736–741.
Riordan J.M., Rommens J.M., Kerem B. et al. 1989. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science. 245, 1066–1073.
Kapranov N.I. 2001. The progress and current problems in diagnostics and treatment of cystic fibrosis in Russia. Pul'monologiya. 11, 9–16.
Ivashchenko T.E., Baranov V.S. 2002. Biokhimicheskie i molekulyarno-biologicheskie osnovy patogeneza mukovistsidoza (Biochemical and Molecular-Biological Bases of Cystic Fibrosis). St. Petersburg: Intermedika.
Drumm M. 2001. Modifier genes and variation in cystic fibrosis. Respir. Res. 2, 125–128.
Prakticheskaya pul'monologiya detskogo vozrasta (spravochnik) (Practical Pulmonology in Children: A Handbook). 2001. Ed. Tatochenko V.K. Moscow: Meditsina.
Tzetis M., Efhtymiadou A., Strofakis S. et al. 2001. CFTR gene mutations including three novel nucleotide substitutions and haplotype background in patients with astma, disseminated bronchiectasis and chronic obstructive pulmonary disease. Human Genet. 108, 216–221.
Mathew C.C. 1984. The isolation of high molecular weight eucaryotic DNA. Methods Molec. Biol. Ed. Walker J.M. NY.: Humana Press, pp. 31–34.
Hayashi S.-I., Watanable J., Kawajiri K. 1992. High susceptibility to lung cancer analyzed in terms of combined genotypes of P450 1A1 and mu-class glutathione S-transferase genes. Jpn. J. Cancer Res. 83, 866–870.
Smith C., Harrison D. 1997. Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema. Lancet. 350, 630–633.
Vavilin V.A., Makarova S.I., Lyakhovich V.V., Gavalov S.M. 2002. Association of the polymorphic genes for xenobiotic biotransformation enzymes with predisposition to bronchial asthma in children with or without hereditary load. Genetika. 38, 539–545.
Lomas D.A., Silverman E.K. 2001. The genetics of chronic obstructive pulmonary disease. Respir. Res. 2, 20–26.
Mace K., Bowman E.D., Vautraverrs P. et al. 1998. Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues. Eur. J. Cancer. 34, 914–920.
Joos l., Pare P., Sanford A. 2002. Genetic risk factors for chronic obstructive pulmonary disease. Swiss Med. Wkly. 132, 27–37.
Koyama H., Gedders D. 1998. Genes, oxidative stress, and the risk of chronic obstructive pulmonary disease. Thorax. 53, 510–514.
Brown R., Wyatt H., Price J. et al. 1996. Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress. Eur. Respir. J. 9, 334–339.
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Korytina, G.F., Yanbaeva, D.G. & Viktorova, T.V. Polymorphisms of the Cytochrome P450 (CYP1A1, CYP2E1) and Microsomal Epoxide Hydrolase (mEPHX) Genes in Cystic Fibrosis and Chronic Respiratory Disease. Molecular Biology 37, 663–670 (2003). https://doi.org/10.1023/A:1026072607702
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DOI: https://doi.org/10.1023/A:1026072607702